Impact of monocyte to high-density lipoprotein ratio on the identification of prevalent coronary heart disease: insights from a general population.

BACKGROUND: Recent studies have identified monocyte to high-density lipoprotein ratio (MHR) as a simple, practical surrogate of atherosclerosis. Considering atherosclerosis is a major mechanism of coronary heart disease (CHD). The present study aims to evaluate the association between MHR and the prevalence of CHD. METHODS AND RESULTS: The present cross-sectional work included 6442 participants (mean age: 59.57 years, 60.2% females), all of them were included from rural areas of northern China between October 2019 to April 2020. MHR was acquired as monocytes count divided by high-density lipoprotein concentration. Prevalent CHD researched 3.14%. After adjustment of sex, age, current drinking and smoking, BMI, WC, diabetes, hypertension, LDL-C, TG, eGFR, lipid-lowering therapy and cerebrovascular disease history, each standard deviation increase of MHR cast a 39.5% additional CHD risk. Furthermore, the top quartile of MHR had an additional 89.0% CHD risk than the bottom quartile. Besides, smooth curve fitting revealed a linear pattern of the association. Additionally, the stratified evaluation showed a robust correlation among the subgroups divided by CHD risk factors. Finally, area under the curve demonstrated an advancement when including MHR into common CHD risk factors (0.744 vs 0.761, p < 0.001). Consistently, reclassification analysis indicated the improvement from MHR (all P = 0.003). CONCLUSION: Our work suggests the robust and linear relationship between MHR and the prevalent CHD in a general population, providing epidemiological evidence for laboratory studies. More importantly, the findings implicate the efficacy of MHR to be a potential indicator to identify the prevalent CHD.

Identifying the role of apolipoprotein A-I in prostate cancer.

Although localized prostate cancer (PCa) can be cured by prostatectomy and radiotherapy, the development of effective therapeutic approaches for advanced prostate cancer, including castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC), is lagging far behind. Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need. Here, we report that apolipoprotein A-I (ApoA-I), the major component of high-density lipoprotein (HDL), is upregulated in PCa based on both bioinformatics and experimental evidence. The fact that advanced PCa shows strong ApoA-I expression reflects its potential role in driving therapeutic resistance and disease progression by reprogramming the lipid metabolic network of tumor cells. Molecularly, ApoA-I is regulated by MYC, a frequently amplified oncogene in late-stage PCa. Altogether, our findings have revealed a novel indicator to predict prognosis and recurrence, which would benefit patients who are prone to progress to metastasis or even NEPC, which is the lethal subtype of PCa.

Marked Changes in Serum Amyloid A Distribution and High-Density Lipoprotein Structure during Acute Inflammation.

High-density lipoprotein- (HDL-) cholesterol measurements are generally used in the diagnosis of cardiovascular diseases. However, HDL is a complicated heterogeneous lipoprotein, and furthermore, it can be converted into dysfunctional forms during pathological conditions including inflammation. Therefore, qualitative analysis of pathophysiologically diversified HDL forms is important. A recent study demonstrated that serum amyloid A (SAA) can remodel HDL and induce atherosclerosis not only over long periods of time, such as during chronic inflammation, but also over shorter periods. However, few studies have investigated rapid HDL remodeling. In this study, we analyzed HDL samples from patients undergoing orthopedic surgery inducing acute inflammation. We enrolled 13 otherwise healthy patients who underwent orthopedic surgery. Plasma samples were obtained on preoperative day and postoperative days (POD) 1-7. SAA, apolipoprotein A-I (apoA-I), and apolipoprotein A-II (apoA-II) levels in the isolated HDL were determined. HDL particle size, surface charge, and SAA and apoA-I distributions were also analyzed. In every patient, plasma SAA levels peaked on POD3. Consistently, the HDL apoA-I : apoA-II ratio markedly decreased at this timepoint. Native-polyacrylamide gel electrophoresis and high-performance liquid chromatography revealed the loss of small HDL particles during acute inflammation. Furthermore, HDL had a decreased negative surface charge on POD3 compared to the other timepoints. All changes observed were SAA-dependent. SAA-dependent rapid changes in HDL size and surface charge were observed after orthopedic surgery. These changes might affect the atheroprotective functions of HDL, and its analysis can be available for the qualitative HDL assessment.

Development and Clinical Application of an Enzyme-Linked Immunosorbent Assay for Oxidized High-Density Lipoprotein.

AIMS: HDL particles have various anti-atherogenic functions, whereas HDL from atherosclerotic patients was demonstrated to be dysfunctional. One possible mechanism for the formation of dysfunctional HDL is the oxidation of its components. However, oxidized HDLs (Ox-HDLs) remain to be well investigated due to lack of reliable assay systems. METHODS: We have developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) for Ox-HDL by using the FOH1a/DLH3 antibody, which can specifically recognize oxidized phosphatidylcholine, a major component of HDL phospholipid (HDL-PL). We defined forced oxidation of 1 mg/L HDL-PL as 1 U/L Ox-HDL. We assessed serum Ox-HDL levels of normolipidemic healthy subjects ( n=94) and dyslipidemic patients (n=177). RESULTS: The coefficients of variation of within-run and between-run assays were 12.5% and 13.5%. In healthy subjects, serum Ox-HDL levels were 28.5±5.0 (mean±SD) U/L. As Ox-HDL levels were moderately correlated with HDL-PL (r=0.59), we also evaluated the Ox-HDL/HDL-PL ratio, which represents the proportion of oxidized phospholipids in HDL particles. In dyslipidemic patients, Ox-HDL levels were highly variable and ranged from 7.2 to 62.1U/L, and were extremely high (50.4±13.3U/L) especially in patients with hyperalphalipoproteinemia due to cholesteryl ester transfer protein deficiency. Regarding patients with familial hypercholesterolemia, those treated with probucol, which is a potent anti-oxidative and anti-hyperlipidemic drug, showed significantly lower Ox-HDL (16.2±5.8 vs. 30.2±5.4, p＜0.001) and Ox-HDL/HDL-PL ratios (0.200±0.035 vs. 0.229±0.031, p=0.015) than those without probucol. CONCLUSION: We have established a novel sandwich ELISA for Ox-HDL, which might be a useful and easy strategy to evaluate HDL functionality, although the comparison study between this Ox-HDL ELISA and the assay of HDL cholesterol efflux capacity remains to be done. Our results indicated that probucol treatment may be associated with lower Ox-HDL levels.

Influence of weight gain on the lipid profile of adolescents / Influencia de la ganancia de peso sobre el perfil lipídico en adolescentes

The objective of this study was to assess the influence of weight gain on the lipid profile of 135 adolescents between 10 - 14 years at baseline and 15 - 19 years at follow-up, enrolled in public schools in Recife, Brazil. The results showed that a BMI z-score correlated with triglycerides (TG) and with high density trigliceride lipopoteine ratio (TG/HDL-c) in males. In females, high z-score correlated with total cholesterol (TC) and low density lipoprotein (LDL-c). In males, for each unit increase in z-score, TG increased by 14.7 mg/dL and the TG/HDL-c ratio increased by 0.4. Among females, TC increased by 9.4 mg/dL, LDL-c increased by 11.6 mg/dL, non-HDL cholesterol increased by 11.8 mg/dL, and HDL-c decreased by 2.3 mg/dL. In males, excessive weight gain was associated with an increase in TG and TG/HDL-c; in females, it was associated with a higher increase in TG/HDL-c and non-HDL cholesterol. However, z-score variation can be a good predictor of lipid profile changes, even in those that are within the normal range.

El objetivo de este estudio fue evaluar la influencia del aumento de peso en el perfil lipídico de 135 adolescentes de edades entre 10 y 14 años de edad al inicio del estudio y de 15 a 19 años en el seguimiento. Los adolescentes pertenecían a escuelas públicas de Recife, Brasil. Los resultados mostraron que el alto puntaje z de indice de masa corporase (IMC) correlacionaba con triglicéridos (TG) y con relación de triglicéridos con lipoproteínas de alta densidad (TG/HDL-c) en los hombres. En las mujeres, puntaje z de IMC se correlacionó con CT y lipoproteína de baja densidad (LDL-c). En los hombres, por cada unidad de aumento en el puntaje z, los TG aumentaron en 14,7 mg/dL y la relación TG / HDL-c aumentó en 0,4; en las mujeres, el CT aumentó en 9,4 mg/dL, el LDL-c aumentó en 11,6 mg/dL, el colesterol no HDL aumentó en 11,8 mg / dL y el HDL-c disminuyó en 2,3 mg/dL. En los hombres, el aumento de peso excesivo se asoció con un aumento de TG y TG/HDL-c; en las mujeres, con un aumento mayor en TG/HDL-c y colesterol no HDL. Sin embargo, la variación z-score puede ser un buen predictor de cambios en el perfil lipídico, incluso en aquellos que se encuentran dentro del rango normal.

Probing the Assembly of HDL Mimetic, Drug Carrying Nanoparticles Using Intrinsic Fluorescence.

Reconstituted high-density lipoprotein (HDL) containing apolipoprotein A-I (Apo A-I) mimics the structure and function of endogenous (human plasma) HDL due to its function and potential therapeutic utility in atherosclerosis, cancer, neurodegenerative diseases, and inflammatory diseases. Recently, a new class of HDL mimetics has emerged, involving peptides with amino acid sequences that simulate the the primary structure of the amphipathic alpha helices within the Apo A-I protein. The findings reported in this communication were obtained using a similar amphiphilic peptide (modified via conjugation of a myristic acid residue at the amino terminal aspartic acid) that self-assembles (by itself) into nanoparticles while retaining the key features of endogenous HDL. The studies presented here involve the macromolecular assembly of the myristic acid conjugated peptide (MYR-5A) into nanomicellar structures and its characterization via steady-state and time-resolved fluorescence spectroscopy. The structural differences between the free peptide (5A) and MYR-5A conjugate were also probed, using tryptophan fluorescence, FÓ§rster resonance energy transfer (FRET), dynamic light scattering, and gel exclusion chromatography. To our knowledge, this is the first report of a lipoprotein assembly generated from a single ingredient and without a separate lipid component. The therapeutic utility of these nanoparticles (due to their capablity to incorporate a wide range of drugs into their core region for targeted delivery) was also investigated by probing the role of the scavenger receptor type B1 in this process. SIGNIFICANCE STATEMENT: Although lipoproteins have been considered as effective drug delivery agents, none of these nanoformulations has entered clinical trials to date. A major challenge to advancing lipoprotein-based formulations to the clinic has been the availability of a cost-effective protein or peptide constituent, needed for the assembly of the drug/lipoprotein nanocomplexes. This report of a robust, spontaneously assembling drug transport system from a single component could provide the template for a superior, targeted drug delivery strategy for therapeutics of cancer and other diseases (Counsell and Pohland, 1982).

Allergic rhinitis is associated with complex alterations in high-density lipoprotein composition and function.

Despite strong evidence that high-density lipoproteins (HDLs) modulate the immune response, the role of HDL in allergies is still poorly understood. Many patients with allergic rhinitis (AR) develop a late-phase response, characterized by infiltration of monocytes and eosinophils into the nasal submucosa. Functional impairment of HDL in AR-patients may insufficiently suppress inflammation and cell infiltration, but the effect of AR on the composition and function of HDL is not understood. We used apolipoprotein (apo) B-depleted serum as well as isolated HDL from AR-patients (n = 43) and non-allergic healthy controls (n = 20) for detailed compositional and functional characterization of HDL. Both AR-HDL and apoB-depleted serum of AR-patients showed decreased anti-oxidative capacity and impaired ability to suppress monocyte nuclear factor-κB expression and pro-inflammatory cytokine secretion, such as interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor alpha and IL-1 beta. Sera of AR-patients showed decreased paraoxonase and cholesteryl-ester transfer protein activities, increased lipoprotein-associated phospholipase A2 activity, while lecithin-cholesterol acyltransferase activity and cholesterol efflux capacity were not altered. Surprisingly, apoB-depleted serum and HDL from AR-patients showed an increased ability to suppress eosinophil effector responses upon eotaxin-2/CCL24 stimulation. Mass spectrometry and biochemical analyses showed reduced levels of apoA-I and phosphatidylcholine, but increased levels of apoA-II, triglycerides and lyso-phosphatidylcholine in AR-HDL. The changes in AR-HDL composition were associated with altered functional properties. In conclusion, AR alters HDL composition linked to decreased anti-oxidative and anti-inflammatory properties but improves the ability of HDL to suppress eosinophil effector responses.

Elucidating bidirectional relationship between metabolic syndrome and elevated faecal haemoglobin concentration: a Taiwanese community-based cohort study.

OBJECTIVES: To elucidate the bidirectional temporal relationship between elevated faecal haemoglobin (f-Hb) concentration and metabolic syndrome (MetS). DESIGN: A longitudinal cohort study was conducted by utilising data on community-based periodical screening for colorectal cancer with faecal immunochemical test (FIT) and health check-up for MetS. SETTING: Population-based organised integrated service screening in Keelung city, Taiwan. PARTICIPANTS: We enrolled a total of 62,293 community residents aged 40-79 years. MAIN OUTCOMES AND MEASURES: Bidirectional outcomes of FIT-positive and MetS were measured. RESULTS: The presence of MetS at baseline led to a statistically significant 31% elevated risk of being incident FIT-positive (adjusted HR, (aHR)=1.31, 95% CI: 1.14 to 1.51) whereas the effect of those with FIT-positive at baseline on incident MetS was not statistically significant (aHR=1.06, 95% CI: 0.89 to 1.25) after adjusting for relevant confounders. Such an effect was particularly noted for three individual components (abnormal waist circumference, higher fasting plasma glucose and lower high-density lipoprotein). CONCLUSIONS: Our finding on the presence of MetS before FIT-positive based on bidirectional relationship assessment suggests the control of MetS may contribute to reducing the risk of colorectal neoplasia through the early surveillance of f-Hb. However, such a temporal epidemiological finding still needs to be verified by using other external data.

Metabolismo e função das lipoproteínas de alta densidade (HDL) em indivíduos idosos: efeito da presença de diabetes mellitustipo 2 e doença coronária obstrutiva / Metabolism and function of high density lipoprotein (HDL) in the elderly: effects of type 2 diabetes mellitus and coronary artery disease

Introdução: A doença arterial coronária (DAC) decorrente da aterosclerose é uma das principais causas de comprometimento do envelhecimento saudável e sobrevida do idoso.Entre os principais fatores de risco da DAC estão o diabetes mellitus tipo 2 (DM) e as dislipidemias. O HDL-colesterol baixo é fator de risco importante, mas aspectos funcionais e metabólicos da HDL devem ser avaliados, já que esta lipoproteína tem várias ações anti-aterogênicas. Neste sentido, a transferência de lípides de outras lipoproteínas para a HDL, mediada pela proteína de transferência de ésteres de colesterol (CETP), é passo importante na formação e metabolismo da HDL e está relacionada com a presença de DAC. Objetivo: Avaliar o impacto da idade nas transferências de lípides para HDL e outros parâmetros relacionados com o metabolismo da HDL em indivíduos idosos e as mudanças nesses parâmetros em idosos com DAC e com DAC e DM. Métodos: Foram estudados 25 jovens (JOV), 35 idosos sem DAC e sem DM (IDS), 35 idosos com DAC (IDS-DAC) e 34 idosos com DAC e DM (IDS-DAC-DM). Foram determinados perfil lipídico e apolipoproteínas plasmáticas, concentração plasmática da CETP e da lecitina-colesterol aciltransferase (LCAT), composição lipídica e diâmetro da HDL e marcadores inflamatórios. A transferência de colesterol esterificado e livre, fosfolípides e triglicérides para a HDL foi realizada por ensaio "in vitro" com uma nanopartícula marcada com lípides radioativos como partícula doadora de lípides. Após a precipitação química das outras lipoproteínas e da nanopartícula doadora, o sobrenadante contendo HDL foi separadoe medida a radioatividade. Resultados: IDS apresentou IMC maior que JOV. LDL-colesterol e não-HDL-colesterol, IL-6 e IL-8 foram mais altos, IL-1ß mais baixo e a transferência de fosfolípides para a HDL foi maior em IDS do que em JOV, mas as diferenças desapareceram quando corrigidas pelo IMC. Entre IDS-DAC e IDS não houve diferenças nos lípides plasmáticos, mas no IDS-DAC a transferência de colesterol livre, triglicérides e fosfolípides foi menor e a de colesterol esterificado foi maior. A concentração de CETP foi maior no IDS-DAC, onde houve maior % de colesterol esterificado e triglicérides e menor % de fosfolípides na HDL. Em IDS-DAC-DM, apoB foi maior que em IDS-DAC, mas LDL-colesterol foi igual. Houve menor transferência de colesterol esterificado em IDS-DAC-DM comparado a IDS-DAC e maior de fosfolípides. IDS-DAC-DM teve CETP mais baixa e LCAT mais alta do que IDS-DAC. Em IDS-DAC-DM houve menor proporção de colesterol esterificado e livre e maior de fosfolípides na HDL. Marcadores inflamatórios não diferiram entre IDS-DAC-DM e IDS-DAC. Conclusões: As alterações nos parâmetros de transferência de lípides sinalizaram tanto a presença de DAC nos idosos quanto diferenciaram idosos com DAC associada a DM daqueles apenas com DAC. A redução da transferência de colesterol livre nos idosos com DAC é aterogênica, como foi mostrado em trabalho anteriorem indivíduos de 40-50 anos com DAC precoce. Esses dados podem ter aplicação tanto na prevenção quanto na terapêutica da DAC, por meio de medicamentos que modulem a transferência de lípides para a HDL e assim melhorem a função anti-aterogênica desta lipoproteína

Introduction: Coronary artery disease (CAD) resulting from atherosclerosis is one of the main causes of compromised healthy aging and lifespan in elderly people. Amongst the main risk factors for CAD are type 2 diabetes mellitus (DM) and dyslipidemias. Low HDL-cholesterol is an important risk factor, but functional and metabolic aspects of HDL must be evaluated, since this lipoprotein has several anti-atherogenic actions. In this regard, lipid transfer from other lipoproteins to HDL, mediated by cholesteryl ester transfer protein (CETP), is an important step towards the formation and metabolism of HDL and is related to the presence of CAD. Objective: To evaluate the impact of age in lipid transfer to HDL and other parameters related to HDL metabolism in elderly individuals and the changes in these parameters in elderly individuals with CAD and with CAD and DM. Methods: 25 young (YOUNG), 35 elderly without CAD and DM (ELDERLY), 35 elderly with CAD (ELDERLY-CAD) and 34 elderly with CAD and DM (ELDERLY-CAD-DM) subjects were studied. The lipid profile, the apolipoprotein, CETP and lecithin-cholesterol acyltransferase (LCAT) plasma concentration,theHDL lipid composition and diameter and inflammatory markers were evaluated.The transfer of esterified and free cholesterol, phospholipids and triglycerides to HDL was assayed in vitro with a donor lipid nanoparticle labeled with radioactive lipids.After chemical precipitation of the other lipoproteins and the donor lipid nanoparticle, the supernatant containing HDL was separated and the radioactivity was measured. Results: ELDERLY presented greater BMI than YOUNG. LDL-cholesterol and non-HDL-cholesterol, IL-6 and IL-8 were higher, IL-1ß was lower and phospholipid transfer to HDL was higher in ELDERLY than in YOUNG, but the differences disappeared when corrected by BMI. There were no differences in plasmatic lipids between ELDERLY-CAD and ELDERLY, but in ELDERLY-CAD the transfer of free cholesterol, triglycerides and phospholipids was lower and of esterified cholesterol was higher. CETP concentration was higher in ELDERLY-CAD, where there was higher % of esterified cholesterol and triglycerides and lower % of phospholipids in HDL. In ELDERLY-CAD-DM, apo B was higher than in ELDERLY-CAD, but LDL-cholesterol was equal. There was lower transfer of esterified cholesterol in ELDERLY-CAD-DM compared to ELDERLY-CAD and higher transfer of phospholipids. ELDERLY-CAD-DM had lower CETP and higher LCAT than ELDERLY-CAD. In ELDERLY-CAD-DM there was a smaller proportion of esterified and free cholesterol and greater proportion of phospholipids in HDL. Inflammatory markers did not differ between ELDERLY-CAD-DM and ELDERLY-CAD. Conclusions: The alterations in the parameters of lipid transfer not only signalled the presence of CAD in the elderly but also differentiated the elderly with CAD and DM from those with CAD only. The reduction of free cholesterol transfer in the elderly with CAD is atherogenic, as shown in a previous work on individuals of 40-50 years of agewith precocious CAD. This data may be applied both to the prevention and the therapeutics of CAD, by means of medicines that modulate lipid transfer to HDL and thus improve the anti-atherogenic function of this lipoprotein

Effects of curcumin on HDL functionality.

Curcumin, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subsequently, may alleviate hyperlipidemia and atherosclerosis. Plasma HDL cholesterol (HDL-C) is an independent negative risk predictor of cardiovascular disease (CVD). However, numerous clinical and genetic studies have yielded disappointing results about the therapeutic benefit of raising plasma HDL-C levels. Therefore, research efforts are now focused on improving HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to heterogeneity in composition. Consistent with its complexity in composition and metabolism, a wide range of biological activities is reported for HDL, including antioxidant, anti-glycation, anti-inflammatory, anti-thrombotic, anti-apoptotic and immune modulatory activities. Protective properties of curcumin may influence HDL functionality; therefore, we reviewed the literature to determine whether curcumin can augment HDL function. In this review, we concluded that curcumin may modulate markers of HDL function, such as apo-AI, CETP, LCAT, PON1, MPO activities and levels. Curcumin may subsequently improve conditions in which HDL is dysfunctional and may have potential as a therapeutic drug in future. Further clinical trials with bioavailability-improved formulations of curcumin are warranted to examine its effects on lipid metabolism and HDL function.

Social mobility and inflammatory and metabolic markers at older ages: the English Longitudinal Study of Ageing.

BACKGROUND: Since our knowledge of the associations between socioeconomic position (SEP) over the life course and inflammatory and metabolic markers, which are excellent predictors of cardiovascular disease, remains limited, we examined the association between social mobility over the life course and these markers at older ages. METHODS: Our study used cross-sectionally collected data from 6142 participants aged 50 years and older from the English Longitudinal Study of Ageing. We estimated linear and logistic models of the associations between social mobility, using information on childhood and adult SEP, C reactive protein (CRP), fibrinogen, glycated haemoglobin (HbA1c) and high-density lipoprotein (HDL) cholesterol. Our models were gradually adjusted for age, sex, chronic diseases, obesity, physical activity, alcohol consumption, smoking status and depressive symptoms. RESULTS: Participants who experienced upward social mobility had higher CRP, fibrinogen and HbA1c levels compared with those who had stable high SEP over the life course, but lower compared with those who experienced downward social mobility or had stable low SEP. They also had lower HDL levels compared with those who had stable high SEP or downwardly mobile. Adjustment for covariates partially explained the associations between social mobility and CRP and HDL, and fully explained those between social mobility and fibrinogen and HbA1c. CONCLUSIONS: Social mobility is associated with inflammatory and metabolic markers at older ages with some of the observed associations persisting after accounting for covariates. Upward social mobility appears to partially reverse the damaging effect of childhood social disadvantage on inflammatory profiles in older ages.

Human pericoronary adipose tissue as storage and possible supply site for oxidized low-density lipoprotein and high-density lipoprotein in coronary artery.

BACKGROUND: Thickening of the pericoronary adipose tissue (PCAT) is a proven risk factor for coronary artery disease, but it is poorly understood whether PCAT stores pro-atherogenic substances with oxidized low-density lipoprotein (oxLDL) and low-density lipoprotein (LDL), and an anti-atherogenic substance with high-density lipoprotein (HDL) and supply them to the coronary intima. METHODS: Using immunohistochemical techniques, the localization of oxLDL, LDL and HDL in PCAT and its adjacent coronary segments was examined in 30 epicardial coronary arteries excised from 11 human autopsy cases. RESULTS: PCAT stored oxLDL and HDL in all, but LDL rarely, in 77 specimens examined, irrespective of the presence or absence of coronary plaques and underlying disease. The percentage (%) incidence of oxLDL, HDL and LDL deposits in intima was, respectively, 28, 10, 35 in 29 normal segments, 80 (p<0.05 vs. normal segments), 12, 75 in 19 white plaques (growth stage), 57, 36, 90 in 15 yellow plaques without necrotic core (NC; mature stage), and 40, 21, 100 (p<0.05 vs. normal segments) in 14 yellow plaques with NC (end-stage of maturation) as classified by angioscopy and histology. In coronary intima, oxLDL deposited in either a dotted or diffuse pattern whereas HDL and LDL showed diffuse patterns. Dotted oxLDL deposits were contained in CD68(+)-macrophages traversing the border of PCAT and adventitia, external and internal elastic laminae. Diffuse oxLDL and HDL deposits colocalized with intimal vasa vasorum. CONCLUSIONS: The results suggested that, as a hitherto unrecognized supplying route, the human PCAT stores oxLDL and HDL and oxLDL is supplied to coronary intima either by CD68(+)-macrophages or vasa vasorum and HDL by vasa vasorum, and that deposition of oxLDL and HDL in the intima increased with plaque growth but the former decreased while the latter increased further with plaque maturation. Molecular therapy targeting PCAT before plaque maturation could be effective in preventing atherosclerosis.

Dieta cetogênica clássica e modificada: risco cardiometabólico e potencial terapêutico em pacientes pediátricos com epilepsia refratária / Classic and modified ketogenic diet: cardiometabolic risk and therapeutic potential in pediatric patients with refractory epilepsy

A dieta cetogênica (DC) é um tratamento não farmacológico prescrito especialmente para crianças e adolescentes com epilepsia refratária. A composição da dieta cetogênica é baseada no alto teor de gorduras, baixo teor de carboidratos e teor proteico moderado, sendo a produção de corpos cetônicos o mecanismo provável envolvido no controle das crises epilépticas. Apesar dos benefícios clínicos, a relação entre DC e o risco cardiometabólico não está bem estabelecida, especialmente sob os fatores de risco não clássicos. Objetivo: comparar os efeitos da dieta cetogênica clássica com a dieta cetogênica modificada nas subfrações de LDL e HDL, nos marcadores oxidativos, no perfil de apolipoproteinas e no perfil lipídico de crianças e adolescentes com epilepsia refratária, além do efeito clínico no controle da epilepsia. Métodos: Estudo de intervenção com recrutamento de crianças e adolescentes com epilepsia refratária de 1 a 19 anos de ambos os sexos do Instituto da Criança do Hospital das Clínicas da FMUSP. O grupo controle recebeu DC clássica e o grupo caso recebeu a DC modificada com redução em pelo menos 20% de ácidos graxos saturados (AGS) e redução da relação w6/w3 em pelo menos 50% em comparação a DC clássica. Para ambos os grupos foram analisados os seguintes parâmetros bioquímicos no período basal, após 3 meses e 6 meses de DC: perfil lipídico clássico, concentração de ácidos graxos não esterificados (AGNEs), substâncias reativas ao ácido tiobarbitúrico (TBARs), subfrações de lipoproteina de baixa densidade (LDL) e lipoproteína de alta densidade (HDL), e perfil de apolipoproteínas (APOA-I e APOB). Além da avaliação clínica, antropométrica e de consumo alimentar. Resultados: A redução de crises e dos fármacos antiepilépticos foi semelhante entre os grupos. O aumento na concentração de colesterol total (CT) e LDL foi inferior no grupo caso, a Não-HDL manteve-se significativamente menor no grupo caso em comparação ao grupo controle e a relação LDL/APOB foi superior no grupo controle após 6 meses de DC. O percentual de partículas pequenas de LDL apresentou aumento superior em 208% no grupo controle comparado ao grupo caso, e consequentemente o tamanho de LDL apresentou maior redução no grupo controle. A incidência de dislipidemia foi significativamente inferior no grupo caso considerando os pontos de corte para LDL (>=130 mg/dL) e não-HDL (>=145 mg/dL). Não houve diferença entre os grupos na concentração de ácidos graxos não esterificados (AGNES) e substâncias reativas ao ácido tiobarbitúrico (TBARs). Conclusão: A mudança do perfil de gorduras 10 contribuiu para melhora das concentrações de marcadores de risco cardiometabólico (CT, LDL e LDL pequenas) e consequentemente, perfil mais cardioprotetor nos pacientes do grupo caso

The ketogenic diet (KD) is a non-pharmacological treatment especially prescribed to children and adolescentes with refractory epilepsy. The composition of the ketogenic diet is based on the high fat, low carbohydrate and moderate protein. The production of ketone bodies is the probable mechanism involved in the control of epileptic seizures. Despite the clinical benefits, the relationship between KD and cardiometabolic risk is not well established, especially under non-classical risk factors. Objective: to compare the effects of the classical KD with the modified KD on the LDL and HDL subfractions, in oxidative biomarkers, in apolipoprotein profile and lipid profile of children and adolescentes with refractory epilepsy, as well as the clinical effect on control of seizure. Methods: Dietary intervention study with recruitment of children and adolescentes with refractory epilepsy aged 1 to 19 years of both sexes from the Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP. The control group received classical KD and the case group received modified KD with a reduction of at least 20% saturated fatty acids (SFA) and a reduction of the w6/w3 ratio by at least 50% compared to classic KD. For both groups, the following biochemical parameters were analyzed at baseline and after 3 and 6 months of the KD: classical lipid profile, concentration of non-esterified fatty acids (NEFAs), thiobarbituric acid reactive substances (TBARs), low density lipoprotein (LDL) and high density lipoprotein (HDL) subfractions, size LDL, and apolipoprotein profile (APOA-I and APOB). In addition to clinical, anthropometric and food consumption assessment. Results: The reduction of seizures and antiepileptic drugs was similar between the groups. The increase in total cholesterol (TC) and LDL levels was lower in the case group, non-HDL remained significantly lower in the case group compared to the control group and the LDL/APOB ratio was higher in the control group after 6 months of KD. The percentage of small LDL particles showed a 208% higher in the control group than case group. Consequently, the LDL size showed a greater reduction in the control group. The incidence of dyslipidemia was significantly lower in the case group considering cut-off points for LDL (>=130 mg/dL) and non-HDL (>=145 mg/dL). There was no difference between the groups in the NEFAs and TBARs levels. Conclusion: The change in the fatty acids profile contributed to improvement the concentrations of cardiometabolic risk markers (TC, 12 LDL and small LDL), and consequently, a more cardioprotective profile in the patients of case group

Isolating and Quantifying Plasma HDL Proteins by Sequential Density Gradient Ultracentrifugation and Targeted Proteomics.

The sensitivity and specificity of tandem mass spectrometers have made targeted proteomics the method of choice for the precise simultaneous measurement of many proteins in complex mixtures. Its application to the relative quantification of proteins in high-density lipoproteins (HDL) that have been purified from human plasma has revealed potential mechanisms to explain the atheroprotective effects of HDL. We describe a moderate throughput method for isolating HDL from human plasma that uses sequential density gradient ultracentrifugation, the traditional method of HDL purification, and subsequent trypsin digestion and nanoflow liquid chromatography-tandem mass spectrometry to quantify 38 proteins in the HDL fraction of human plasma. To control for the variability associated with digestion, matrix effects, and instrument performance, we normalize the signal from endogenous HDL protein-associated peptides liberated during trypsin digestion to the signal from peptides liberated from stable isotope-labeled apolipoprotein A-I spiked in as an internal standard prior to digestion. The method has good reproducibility and other desirable characteristics for preclinical research.

Avaliação de aspectos funcionais da lipoproteína de alta densidade (HDL) e suas subfrações em pacientes com doença arterial coronária / Evalution of functional aspects from high density lipoproteins (HDL) and their subfractions from coronary heart disease patients

Estudos clínicos e epidemiológicos indicam que baixas concentrações plasmáticas da lipoproteína de alta densidade (HDL) estão forte e independentemente associadas a uma maior incidência de doença arterial coronária (DAC). Entretanto, o insucesso dos agentes que são capazes de aumentar a concentração de HDL-C sugere que a funcionalidade da HDL pode representar um alvo terapêutico mais apropriado. Para a avaliação de um dos aspectos funcionais da HDL, o presente trabalho descreve o desenvolvimento de um método de grande praticidade que permite uma visão integrada de uma etapa fundamental do metabolismo que é a transferência de lípides entre as diferentes classes de lipoproteínas. A avaliação deste fenômeno nas subfrações de HDL, aspecto ainda não explorado, poderá fornecer novas informações a respeito da fisiopatologia da DAC. O método descrito no presente trabalho permite a avaliação da transferência simultânea das quatro principais classes lipídicas doadas por uma nanoemulsão semelhante à LDL para a HDL3. Foi realizada análise dos possíveis interferentes neste método. Verificou-se que a elevação da temperatura de 0 a 40 °C resultou em aumento progressivo na transferência de todos os lipídeos para a HDL3. A variação de pH entre 6,5 e 8,5 e o aumento na concentração de albumina não alteraram os valores de transferência. O aumento no tempo de incubação acima de 60 minutos promoveu diminuição na transferência de colesterol esterificado para a HDL3 e aumento na transferência de fosfolipídeos. O método apresentou boa precisão intra e inter-ensaio, sendo o coeficiente de variação menor que 5% para todos os lipídeos. A porcentagem média de transferência de colesterol livre, fosfolipídeos, triacilglicerol e colesterol em 45 invíduos saudáveis foi de respectivamente de 1,1±0,06; 13,5±0,15; 2±0,05 e 0,84±0,04% e em 45 portadores de doença arterial coronária foi respectimente 1,0±0,04; 15,8±0,44; 1,77±0,04 e 1,0±0,06%. Não houve diferença nos valores de idade, IMC, colesterol total, HDL-C, LDL-C, triacilglicerol, apo A-1, apo B, CETP, PLTP e LCAT, mas os indivíduos portadores de doença arterial coronária apresentaram valores maiores de colesterol livre e colesterol total em relação aos indivíduos saudáveis. O método desenvolvido no presente estudo é prático, preciso e de potencial relevância como ferramenta no estudo dos distúrbios de função da HDL

Clinical and epidemiological studies show that low concentrations of high density lipoproteins (HDL) are strongly and independently associated to an increased incidence of coronary artery disease (CAD). However, the lack of success of some drugs developed to increase HDL cholesterol concentrations (HDL-C) suggests that the functional aspects of HDL may represent a more appropriate therapeutic target. To study one of the functional aspects of HDL, the present work describes the development of a practical method that provides an integrated view of a fundamental step of lipid metabolism, namely, the lipid transfer among different lipoprotein classes. This phenomenon in the HDL subfractions is yet unexplored, and could provide new insights on the pathophysiology of CAD. The method described here allows the measurement of the ability of HDL3 to receive the major lipid classes from a radioactively labeled nanoparticle that resemble LDL. The possible interfering factors at the lipid transfer to HDL3 were studied. The increase in the assay temperature from 0 to 40 °C results in a progressive increase in the net transfer of all lipids to HDL3. The increase in incubation time above 60 minutes resulted in a reduced transfer of cholesterol esters to HDL3 with a concomitant increase in the transfer of phospholipids to the latter. The method presented adequate intra and inter-assay precision, with a coefficient of variation smaller than 5% for all lipids. The average percentage of free cholesterol, phospholipids, triacilglycerol an cholesterol transfer to HDL3 was respectively of 1,1±0,06; 13,5±0,15; 2±0,05 e 0,84±0,04% in 45 healthy individuals and 1,0±0,04; 15,8±0,44; 1,77±0,04 e 1,0±0,06% in 45 CAD patients. There was no difference in the age, BMI, total cholesterol, HDL-C, LDL-C, triacilglycerol, apo A-1, apo B, CETP, PLTP and LCAT but the CAD patients had higher levels of total cholesterol and free cholesterol. The method described here is practical, precise and potentially relevant as a tool to study HDL function

Remodelamento de partículas lipoprotéicas de alta densidade (HDL) e atividade antioxidante entre pacientes diabéticos e não diabéticos com doença aterosclerótica coronária / Remodeling of high-density lipoprotein particles (HDL) and antioxidant activity between diabetic and non-diabetic patients with coronary artery disease

sendo a doença aterosclerótica a de maior morbimortalidade. Além disso, a aterosclerose pode manifestar-se precocemente dada a presença de dislipidemias, processos inflamatórios e alterações metabólicas como a diabetes. OBJETIVO: avaliar se existem diferenças no remodelamento da HDL e atividade antioxidante entre pacientes diabéticos e não diabéticos com doença aterosclerótica. Ainda, identificar, quantificar e estimar biomarcadores relacionados ao remodelamento de partículas lipoprotéicas e ao risco cardiovascular em função da concentração de colesterol na HDL, colesterol livre total,LDL-C, apoB, apoA-I, atividade da paraoxonase 1 (PON1), razões de risco como TG/HDL-C, LDL-C/ApoB, HDL-C/apoA-I, PON1/apoA-I, apoA-I/ApoB e tamanho estimado de partículas de HDL, LDL, glicemia, insulina e HbA1c. MÉTODOS: foram selecionados por conveniência 69 pacientes do sexo masculino, entre 18 e 75 anos,oriundos da enfermaria de cardiologia do Hospital Ana Neri, subdivididos em dois subgrupos: diabéticos e não diabéticos, ambos, com doença aterosclerótica coronária.Foram utilizadas metodologias enzimáticas, imunoturbidimétricas e nefelometricas nesse estudo. RESULTADOS: dos achados da comparação direta entre os grupos apenas a glicemia de jejum foi significativamente diferente (Teste t; p<0,05). Embora não significante o valor do colesterol não esterificado (CL) foi, em média, quatro vezes maior nos diabéticos quando comparado aos não diabéticos. A análise de correlação linear mostrou achados importantes do ponto de vista fisiológico, como correlação positiva entre CL e HDL-C (r=0,617; p<0,01083) e razão apoA-I/apoB e insulina (r=0,489; p<0,02095) nos diabéticos, e correlação negativa entre PON1/apoA-I com CL (r=-0,499; p<0,0065) e HDL-C com HbA1c (r=-0,444; p<0,0324) nos pacientes não diabéticos. CONCLUSÃO: Os achados desse estudo mostram que o cálculo das razões utilizadas para a análise de risco cardiovascular foram importantes indicadores quando correlacionados com marcadores séricos sugestivos de risco cardiovascular na população masculina diabética deste estudo.

Introduction: cardiovascular diseases affect thousands of people around the world, and atherosclerotic disease is the one with the greatest morbidity and mortality. Furthermore, atherosclerosis may manifest early by the presence of dyslipidemia, inflammatory processes and metabolic disorders such as diabetes. Objective: to assess whether there are differences between HDL remodeling and antioxidant activity from diabetic and nondiabetic patients with coronary artery disease. Also, identify, quantify and evaluate biomarkers related to lipoprotein particles remodeling and cardiovascular risk depending on HDL cholesterol concentration, total free cholesterol, LDL-C, apoB, apoA-I, paraoxonase activity 1 (PON1), and risk ratios like TG/HDL-C, LDL-C/ApoB, HDLC/apoA-I, PON1/apoA-I, apoA-I/ApoB, HDL and LDL estimated particles size, glucose, insulin and HbA1c. Methods: we selected by convenience 69 male patients between 18 and 75 years, from the Cardiology Unit of Hospital Ana Neri, they were subdivided into two groups: diabetic and non-diabetic patients, both with coronary atherosclerosis. In these study were used enzymatic, immunoturbidimetric and nephelometric methodologies. Results: From the findings of the direct comparison between groups only fasting glucose was significantly different (t test; p <0.05). Although not significant, the value of non-esterified cholesterol (CL) was on average, four times higher in diabetics when compared to non-diabetics. Linear correlation analysis showed significant findings, from a physiological point of view, as positive correlation between CL and HDL-C (r = 0.617, p <0.01083) and apoA-I ratio/apoB and insulin (r = 0.489, p <0.02095) in diabetics, and negative correlation between PON1/apoA-I with CL (r = -0.499; p <0.0065) and HDL-C with HbA1c (r = -0.444; p <0.0324) in patients non-diabetic. Conclusion: the findings shows that the calculated ratio´s used for cardiovascular risk analysis were important indicators when correlated to serum markers suggestive of cardiovascular risk in the study diabetic male population.

Papel do ômega-3 nas características físico-químicas da HDL e LDL e possível associação com medidas Z-scan em indivíduos adultos / Role of omega-3 on HDL and LDL physicochemical characteristics and possible association with Z-scan measurements in adults

Introdução: O aumento na prevalência das doenças cardiovasculares alerta para a necessidade de estratégias eficazes e de baixo custo como medidas preventivas na redução dos fatores de risco, morbidades e óbitos decorrentes de eventos coronarianos. As modificações no estilo de vida são as primeiras alternativas a serem adotadas. Nesse contexto, a dieta ocupa lugar de destaque e os benefícios dos ácidos graxos poli-insaturados ômega-3 na saúde cardiovascular são amplamente reconhecidos. As doenças cardiovasculares são influenciadas por diversos fatores de risco e o desequilíbrio na concentração plasmática das lipoproteínas é um fator de risco independente no desenvolvimento da doença cardiovascular aterosclerótica. Entretanto, há evidências de que as subfrações lipoproteicas podem influenciar o risco cardiovascular de maneira diferenciada, dependendo das características físico-químicas e funcionalidade de cada partícula. O desenvolvimento de novas técnicas, capazes de identificar esses parâmetros, tem sido foco de grande interesse científico. Objetivo: Avaliar o papel do ômega-3 sobre as características físico-químicas da LDL e HDL e possível associação entre medidas Z-scan e marcadores cardiometabólicos em indivíduos adultos. Metodologia: A partir de uma subamostra do estudo CARDIONUTRI (estudo clínico, randomizado, controlado e duplo cego com seguimento de 8 semanas) foram selecionados 36 indivíduos do Grupo Ômega-3 (3,0g/dia de óleo de peixe - 1,11g de EPA + 0,69g de DHA) e 27 do Grupo Placebo (3,0g/dia de óleo mineral). Foram monitorados o perfil clínico, antecedentes familiares, consumo alimentar, atividade física e antropometria. Amostras de sangue foram coletadas após 12 horas de jejum para avaliação das concentrações plasmáticas de CT, TAG, HDL-C, LDL-C, APOAI, APOB, PON1 e glicose. O tamanho da HDL e LDL foi analisado pelo método padronizado Lipoprint®. O conteúdo de LDL(-) foi determinado por ELISA. As medidas Z-scan foram determinadas por meio da difusividade térmica e absorção linear da LDL (1,0 mg/dL de proteína), isolada por ultracentrifugação. Todos as variáveis do estudo foram avaliadas no momento basal e após 8 semanas de intervenção. A adesão à intervenção foi monitorada pela contagem de cápsulas e percentual dos ácidos graxos plasmáticos. Para avaliar a associação das medidas Z-Scan aos marcadores cardiometabólicos, os dados obtidos no momento basal foram submetidos à Análise de Componentes Principais. Resultados: A idade média dos participantes do estudo foi de 51,5 (10,5) anos. A suplementação com ômega-3 promoveu redução significativa de CT, TAG, não-HDL, HDLPEQUENA e LDL(-), além de aumento significativo de HDL-C e HDLGRANDE. O ômega-3 foi mais eficaz na redução dos TAG (29,2 por cento ) quando comparado ao placebo (2,9 por cento ). O Grupo Ômega-3 apresentou aumento de HDLGRANDE (16,9 por cento ) e redução de HDLPEQUENA (-16,3 por cento ) ao final da intervenção, com diferença significativa quando comparado ao Grupo Placebo que apresentou redução de HDLGRANDE (-4,8 por cento ) e aumento de HDLPEQUENA (17,7 por cento ). Não foram observadas diferenças nas medidas Z-scan após a intervenção, porém as medidas se associaram positivamente a Componentes Principais com padrões cardioprotetores da amostra e negativamente a padrões aterogênicos. Conclusão: O ômega-3 demonstrou efeito positivo no perfil lipídico e propriedades aterogênicas das subfrações lipoproteicas. A suplementação com ômega-3 não modificou as medidas Z-scan, no entanto, a técnica demonstrou ser uma ferramenta capaz de se associar a padrões aterogênicos e antiaterogênicos monitorados no presente estudo.

Introduction: The increased of cardiovascular disease prevalence draws attention to the need to adopt effective and inexpensive strategies as preventive measures to reduce risk factors, morbidity and deaths from coronary events. Lifestyle modification is indicated as first alternative to be adopted. In this context the diet stands out and omega-3 polyunsaturated fatty acids benefits on cardiovascular health are largely recognized. Cardiovascular diseases are influenced by several risk factors and the plasma imbalance lipoprotein is considered a crucial independent risk factor. However, there is evidence of the influence of lipoprotein subfractions in cardiovascular risk, based on the physicochemical characteristics of these particles. The development of new techniques able to identify those parameters has been the focus of great scientific interest. Objective: To evaluate the role of omega-3 on HDL and LDL physicochemical characteristics and possible association between Z-scan measurements and cardiometabolic markers in adults. Methods: From a subsample of the study CARDIONUTRI (clinical, randomized, controlled, double blind study with 8-week follow-up) were selected 36 individuals from the Omega-3 Group (3.0g/day of fish oil - 1,11g EPA + 0.69g DHA) and 27 individuals from the Placebo Group (3.0g/day of mineral oil). The clinical profile, family history, dietary intake, physical activity and anthropometry were monitored. Blood samples were collected after 12 hours of fasting to evaluate plasma concentrations of TC, TAG, HDL-C, LDL-C, APOAI, APOB, PON1 and glucose. The HDL and LDL size was analyzed by the standard method Lipoprint®. The levels of LDL (-) was determined by ELISA. The Z-scan measurements were determined by thermal diffusivity and linear absorption of LDL (1.0 mg / dL protein) isolated by ultracentrifugation. All study variables were evaluated at baseline and after 8 weeks of intervention. The intervention accession was monitored by capsule count and percentage of plasma fatty acids. To evaluate the association of the Z-Scan measurements to cardiometabolic markers, the data collected at baseline were subjected to Principal Component Analysis. Results: The average age of individuals were 51.5 (10.5) years. The omega-3 supplementation promoted a significant decreased of TC, TAG, non-HDL, small HDL and LDL(-), and significantly increased HDL-C and large HDL. The omega-3 was more effective in reducing the TAG (29.2 per cent ) when compared to placebo (2.9 per cent ). The Omega-3 Group increased large HDL (16.9 per cent ) and decreased small HDL (-16.3 per cent ) after the intervention, with significant difference when compared to the Placebo Group that decreased large HDL (-4.8 per cent ) and increased small HDL (17.7 per cent ). There were no differences in Z-scan measurements with the interventions, but were observed positively associated the Z-scan measurements with the anti-atherogenic sample patterns and negatively associated with atherogenic sample patterns when the sample was standardized from the Principal Components Analysis. Conclusion: The omega-3 demonstrated positive effect on the lipid profile and atherogenic lipoprotein subfractions. Supplementation with omega-3 did not modify the Z-scan measurements, however, the technique proved to be a tool that can be associated with atherogenic and anti-atherogenic sample patterns monitored in this study.

Efeito da administração In Bolus da heparina sódica no remodelamento de partículas lepoprotéicas associadas ao transporte reverso do colesterol / In bolus administration the effect of heparin sodium in remodeling lepoprotéicas particles associated with reverse cholesterol transport

Introdução: as doenças cardiovasculares acometem milhares de pessoas no mundo. Destas, a doença arterosclerótica está entre as de maior morbimortalidade. Para a avaliação da necessidade de intervenções hemodinâmicas e/ou revascularização miocárdica, há a necessidade da realização do cateterismo (CATE), procedimento de imagem indicado para evidenciar pontos de obstrução e determinar a melhor estratégia cirúrgica. Para a realização do CATE utiliza-se heparina sódica (5000 UI) in bolus. Atualmente, sabe-se que a heparina interfere no remodelamento de partículas lipoproteicas por liberação da lipoproteína lipase (LPL) e da lipase hepática (LH), essa ação pode alterar o transporte reverso do colesterol (TRC), em função de modificações no metabolismo das lipoproteínas. Métodos: foram selecionados por conveniência 20 pacientes, 10 do sexo masculino e 10 do sexo feminino, ambos os sexos, entre 45 e 73 anos, admitidos no Hospital Ana Neri, submetidos à cineangiocoronariografia (CATE)...

Introduction: cardiovascular diseases affect thousands of people worldwide. Of these, the atherosclerotic disease is one of the most morbidity and mortality. To evaluate the need for hemodynamic interventions and / or CABG, the catheterization (CATE) is performed, an imaging procedure to evidence obstruction and to determine the best surgical strategy. To perform CATE, is necessary to use in bolus sodium heparin (5000 IU). Currently, it is known that heparin interferes with the remodeling of the lipoprotein particles by releasing lipoprotein lipase (LPL) and hepatic lipase (HL), this action may alter the reverse cholesterol transport (TRC), by changes in lipoprotein metabolism. Methods: were selected by convenience 20 patients, 10 male and 10 female, both gender, between 45 and 73 years old, admitted to the Hospital Ana Neri, who underwent coronary angiography (CATE)...

Nitric oxide production, systemic inflammation and lipid metabolism in periodontitis patients: possible gender aspect.

AIM: Nitric oxide (NO) plays a crucial role in vascular tone regulation and is involved in pathogenesis of periodontitis. In this cross-sectional study, we investigated the serum and saliva levels of NO metabolites in periodontal disease and their relationship with serum C-reactive protein (CRP) levels, lipids metabolism and periodontal disease severity. MATERIAL AND METHODS: Serum and saliva were collected from non-smoking patients with generalized severe periodontitis (n = 89) and healthy controls (n = 56). Serum and salivary levels of NO metabolites, serum levels of high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides, cholesterol and CRP were measured. Data were analysed in whole population and in different gender groups. RESULTS: Periodontitis patients exhibited significantly lower serum and saliva levels of NO metabolites and significantly higher LDL, cholesterol and CRP levels than control group. Similar findings were observed within male but not within female population. Serum NO metabolites levels exhibited significant negative correlation with CRP in whole population and in male population. Significant positive correlation of serum NO metabolite levels with HDL levels was observed in whole population. CONCLUSION: NO production is reduced in periodontitis, especially in male population. Gender might be an important factor in assessing risk of cardiovascular disease in periodontitis.