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1.
PLoS One ; 15(8): e0237739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817629

RESUMO

OBJECTIVE: To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients. METHODS: We performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/µL, not starting c-ART; and group B, CD4<500 cells/µL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time. RESULTS: The study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30-43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values. CONCLUSIONS: In treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.


Assuntos
Aterosclerose/sangue , Biomarcadores/sangue , Infecções por HIV/sangue , Lipídeos/sangue , Adulto , Antirretrovirais/administração & dosagem , Antirretrovirais/sangue , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Aterosclerose/tratamento farmacológico , Aterosclerose/virologia , Proteína C-Reativa/metabolismo , Espessura Intima-Media Carotídea , Colesterol/sangue , Grupos Controle , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/virologia , Lipoproteínas LDL/sangue , Masculino , Estudos Prospectivos
2.
Gene ; 762: 145019, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32755657

RESUMO

Dyslipidemia is a well-established risk factor for cardiovascular disease. Experimental studies have reported that peroxisome proliferator-activated receptor γ (PPAR-γ) regulates adipocyte differentiation, lipid storage, and glucose metabolism. Therefore, we examined the associations between PPAR-γ polymorphisms (rs1801282, rs3856806, rs12497191, rs1151999, and rs1152003) and serum lipids in two cross-sectional studies. In the Shizuoka area of the Japan Multi-Institutional Collaborative Cohort Study, we examined 4,952 participants (3,356 men and 1,596 women) in a baseline survey and 2,245 participants (1,550 men and 695 women) in a second survey 5 years later. Outcome measures were the prevalence of dyslipidemia (low-density lipoprotein-cholesterol [LDL-C] ≥ 140 mg/dl, high-density lipoprotein-cholesterol < 40 mg/dl, triglycerides ≥ 150 mg/dl, and/or use of cholesterol-lowering drugs) and the prevalence of high LDL-C (LDL-C ≥ 140 mg/dl and/or use of cholesterol-lowering drugs). Multivariate odds ratios (ORs) were estimated by using unconditional logistic regression models. A total of 2,114 and 1,431 individuals (42.7% and 28.9%) had dyslipidemia and high LDL-C in the baseline survey, respectively, as did 933 and 716 (41.6% and 31.9%), respectively, in the second survey. In the baseline study, compared with major allele homozygotes, minor allele homozygotes of rs3856806 and rs12497191 had a 42% (OR, 0.58; 95% confidence interval (CI), 0.39-0.85) and 23% (OR, 0.77; 95% CI, 0.60-0.99) lower risk of dyslipidemia, respectively, after adjustment for potential confounding factors. In addition, minor allele homozygotes of rs3856806 had a 45% (OR, 0.55; 95% CI, 0.35-0.86) lower risk of high LDL-C. Similar risk reductions were found in the second survey. In conclusion, rs3856806 and rs12497191 polymorphisms may be related to a lower risk of dyslipidemia and high LDL-C.


Assuntos
Dislipidemias/genética , PPAR gama/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Colesterol/sangue , Dislipidemias/sangue , Feminino , Humanos , Vida Independente , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade
3.
PLoS One ; 15(8): e0237148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745152

RESUMO

The susceptibility to cardiovascular disease in offspring could be reduced prior to birth through maternal intervention, before and during pregnancy. We evaluated whether the initiation periods of maternal exercise in preconception and pregnancy periods induce beneficial effects in the adult male offspring. Thirty-two female rats were divided into control and exercise groups. The exercise groups involve exercise before pregnancy or the preconception periods, exercise during pregnancy, and exercise before and during pregnancy. The mothers in the exercise groups were run on the treadmill in different periods. Then the birth weight and weekly weight gain of male offspring were measured, and the blood and left ventricle tissue of samples were collected for analysis of the Sirtuin 6 (Sirt6) and insulin growth factor-2 (IGF-2) gene expression, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol (Cho), and triglycerides (TG). There was no significant difference in the birth weight of offspring groups (P = 0.246) while maternal HIIT only during pregnancy leads to reduce weekly weight gain of offspring. Our data showed that Sirt6 and IGF-2 gene expression was increased (P = 0.017) and decreased (P = 0.047) by maternal exercise prior to and during pregnancy, respectively. Also, the serum level of LDL (p = 0.002) and Cho (P = 0.007) were significantly decreased and maternal exercise leads to improves the running speed of the adult male offspring (p = 0.0176). This study suggests that maternal HIIT prior to and during pregnancy have positive intergenerational consequence in the health and physical readiness of offspring.


Assuntos
Metabolismo dos Lipídeos , Miocárdio/metabolismo , Condicionamento Físico Animal/métodos , Sirtuínas/genética , Animais , Peso ao Nascer , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Feminino , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Lipoproteínas LDL/sangue , Masculino , Gravidez , Ratos , Ratos Wistar , Sirtuínas/metabolismo , Triglicerídeos/sangue
4.
Medicine (Baltimore) ; 99(28): e21162, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664153

RESUMO

Small dense low-density lipoprotein (sdLDL) is a distinct low-density lipoprotein (LDL) cholesterol subclass that has been reported to be associated with metabolic disease. On the other hand, the relationship between the sdLDL level and the nonalcoholic fatty liver disease (NAFLD) severity is unclear. In this study, the sdLDL level was measured in patients with NAFLD to assess its potential as a biomarker for evaluating NAFLD. One hundred and twenty-six patients diagnosed with NAFLD at a single referral hospital from January 2018 to August 2019 were enrolled. The lipoprotein profile was analyzed from a blood test of NAFLD patients, and transient elastography (TE, Fibroscan) was performed to evaluate the degree of NAFLD. Among the 126 patients, 83 patients that could confirm the lipoprotein profile and TE results were finally enrolled in the study. The controlled attenuation parameter (CAP) value obtained from TE did not show any correlation with the total cholesterol, LDL. But, the sdLDL level showed a significant positive correlation with the CAP value (r = 0.237, P = .031), and the sdLDL/LDL ratio also showed a significant positive correlation with the CAP value (r = 0.235, P = .032). The liver stiffness (LS) measured by TE and the sdLDL level were positively correlated in patients with NAFLD (rho = 0.217, P = .049). The sdLDL/LDL ratio also showed a significant positive correlation with the LS value (rho = 0.228, P = .038). In addition, the fatty liver index also showed a significant positive correlation with the sdLDL/LDL ratio (r = 0.448, P = .000). In this study, the sdLDL level measured by a blood test of NAFLD patients showed a positive correlation with the CAP value and LS, which indicate the degree of hepatic steatosis and fibrosis. These results suggest the possibility of the sdLDL level as a new biomarker of NAFLD, but further studies will be needed to support these results.


Assuntos
Lipoproteínas LDL/sangue , Testes de Função Hepática/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Índice de Gravidade de Doença , Adulto , Biomarcadores/sangue , Técnicas de Imagem por Elasticidade/estatística & dados numéricos , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco
5.
Arterioscler Thromb Vasc Biol ; 40(9): 2310-2321, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32611242

RESUMO

OBJECTIVE: Plant stanol ester supplementation (2-3 g plant stanols/d) reduces plasma LDL (low-density lipoprotein) cholesterol concentration by 9% to 12% and is, therefore, recommended as part of prevention and treatment of atherosclerotic cardiovascular disease. In addition to plasma LDL-cholesterol concentration, also qualitative properties of LDL particles can influence atherogenesis. However, the effect of plant stanol ester consumption on the proatherogenic properties of LDL has not been studied. Approach and Results: Study subjects (n=90) were randomized to consume either a plant stanol ester-enriched spread (3.0 g plant stanols/d) or the same spread without added plant stanol esters for 6 months. Blood samples were taken at baseline and after the intervention. The aggregation susceptibility of LDL particles was analyzed by inducing aggregation of isolated LDL and following aggregate formation. LDL lipidome was determined by mass spectrometry. Binding of serum lipoproteins to proteoglycans was measured using a microtiter well-based assay. LDL aggregation susceptibility was decreased in the plant stanol ester group, and the median aggregate size after incubation for 2 hours decreased from 1490 to 620 nm, P=0.001. Plant stanol ester-induced decrease in LDL aggregation was more extensive in participants having body mass index<25 kg/m2. Decreased LDL aggregation susceptibility was associated with decreased proportion of LDL-sphingomyelins and increased proportion of LDL-triacylglycerols. LDL binding to proteoglycans was decreased in the plant stanol ester group, the decrease depending on decreased serum LDL-cholesterol concentration. CONCLUSIONS: Consumption of plant stanol esters decreases the aggregation susceptibility of LDL particles by modifying LDL lipidome. The resulting improvement of LDL quality may be beneficial for cardiovascular health. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01315964.


Assuntos
Dieta , Ésteres/administração & dosagem , Hipercolesterolemia/dietoterapia , Lipoproteínas LDL/sangue , Fitosteróis/administração & dosagem , Agregados Proteicos , Adulto , Idoso , Biomarcadores/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Finlândia , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Lipidômica , Masculino , Pessoa de Meia-Idade , Proteoglicanas/sangue , Esfingomielinas/sangue , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangue , Adulto Jovem
6.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(6): 839-844, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32564546

RESUMO

Objective: To quantitatively analyze the death and disability-adjusted life years (DALY) attributed to high level serum LDL-C in Chinese population in 2017. Methods: Data were obtained from the '2017 Global Burden of Disease Study (GBD2017)'. Population attributable fraction (PAF), number and rate of deaths and DALY attributable to high LDL-C were used to describe the burden of disease by gender, age groups, diseases and provinces in China. Both rates on mortality and DALY were standardized by GBD world population. Results: In 2017, 862 759 deaths were caused by high level serum LDL-C in China, that accounting for 8.25% of the total deaths. Of the attributable deaths, 705 355 (81.76%) persons died from ischemic heart disease (IHD), while the remaining 18.24% from ischemic stroke (IS). High LDL-C accounted for 40.30% of the total deaths from ischemic heart disease and 18.49% from ischemic stroke. The highest PAF of death (13.70%) appeared in Jilin province and the lowest in Zhejiang province (4.65%). PAF of death was seen higher in females than in males, while both age-standardized rates of mortality and DALY appeared higher in males than in females. High LDL-C attributed mortality rate appeared as 61.08/100 000 after standardization in Chinese population. High LDL-C attributed DALYs were 18.16 million person years, among which 76.76% were caused by IHD (13.94 million person years), with DALY rate as 1285.83/100 000. Among provinces, Heilongjiang showed the highest standardized DALY rate, and Zhejiang the lowest. The PAF, number of deaths, rates on mortality and DALY caused by high LDL-C were high among residents above 70 years old, with the DALY number as 8.56 million person years, highest seen in the age group from 50 to 69 years old. Conclusion: The burden of disease attributed to high level LDL-C was quite high and with gender, age group and interprovincial differences, in China in 2017.


Assuntos
Efeitos Psicossociais da Doença , Pessoas com Deficiência/estatística & dados numéricos , Lipoproteínas LDL/sangue , Mortalidade/tendências , Anos de Vida Ajustados por Qualidade de Vida , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
PLoS One ; 15(6): e0234639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525924

RESUMO

BACKGROUND AND AIM: Kratom, or Mitragyna speciosa Korth., is a tropical plant that has been reported to exhibit opioid-like effects. Although opioids have been demonstrated to alter the lipid profile of regular users, data on the lipid-altering effects of kratom are scarce. This study aimed to compare the fasting lipid profile of regular kratom users to that of healthy subjects who do not use kratom. It also determined the association between various characteristics of kratom users and the serum triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels of regular kratom users. METHODS: A total of 200 participants (n = 100 kratom users and n = 100 healthy subjects who do not use kratom) were recruited for this analytical cross-sectional study. Data on sociodemographic status, kratom use characteristics, cigarette smoking, physical activity, body mass index (BMI), fasting serum lipid profile, and liver function were collected from all participants. RESULTS: The liver parameters of the study participants were within normal range. The serum total cholesterol and LDL of kratom users were significantly lower than those of healthy subjects who do not use kratom. There were no significant differences in the serum triglyceride and HDL levels. However, higher average daily frequency of kratom use and increasing age were associated with increased serum total cholesterol among kratom users. Other kratom use characteristics such as age of first kratom intake, duration of kratom use, and quantity of daily kratom intake were not associated with increased serum triglyceride, total cholesterol, LDL, and HDL levels. CONCLUSIONS: Our findings suggest regular kratom consumption was not linked to elevated serum lipids, except when there is a higher frequency of daily kratom intake. However, the study was limited by the small sample size, and hence a more comprehensive study with larger sample size is warranted to confirm the findings.


Assuntos
Alcaloides/farmacologia , Drogas Ilícitas/farmacologia , Metabolismo dos Lipídeos , Mitragyna/química , Extratos Vegetais/farmacologia , Adulto , Estudos de Casos e Controles , Colesterol/sangue , Feminino , Humanos , Vida Independente , Lipoproteínas LDL/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Triglicerídeos/sangue
8.
Medicine (Baltimore) ; 99(26): e20817, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590767

RESUMO

RATIONALE: Although there are several reports on the effect of herbal medicine on weight loss in adults, evidence supporting its efficacy and safety in obese pediatrics is insufficient. Herein, we clinically investigated the preliminary experience of community-based healthcare program in cases of childhood obesity treated with an herbal complex, Slim-diet (SD), along with lifestyle modification. PATIENT CONCERNS: Seventeen subjects with childhood obesity participated in a community-based healthcare program, which consisted of twice-a-week play type physical activity and dietary counseling program with simultaneous twice-a-day administration of SD for 4 weeks. DIAGNOSES: The data of 13 obese pediatrics (body mass index [BMI] ≥ the 95th percentile for children of the same age and sex) in their 3rd to 6th grade who finally completed at least 6 visits out of a total of 8 visits of the program including baseline and endpoint assessments were analyzed. INTERVENTIONS: Participants received 20 g of SD daily. Simultaneously, play-type physical activity program with an exercise therapist and dietary counseling with a dietitian for lifestyle modification were conducted at every visit. Body composition, blood chemistry, the Korean Youth Physical Activity Questionnaire (KYPAQ) score, and the preference for salt density and sugar content were assessed at baseline and endpoint. OUTCOMES: After SD administration, body mass index decreased from 26.74 ±â€Š2.11 kg/m to 26.50 ±â€Š2.20 kg/m (P < .05) with statistically significant increases in height, weight, and skeletal muscle mass. The results of blood chemistry and the KYPAQ score showed no significant change. The preferences for salt density were improved in 8, maintained in 2, and worsened in 3 participants and those for sugar content were improved in 6 and maintained in 7 participants with no worsening. LESSONS: In the present study, we showed the clinical effects of SD with lifestyle modification in patients with childhood obesity who participated in community-based healthcare program. Further clinical studies investigating the effects of SD are required.


Assuntos
Dieta Redutora/normas , Obesidade Pediátrica/dietoterapia , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Dieta Redutora/métodos , Feminino , Humanos , Lipoproteínas LDL/análise , Lipoproteínas LDL/sangue , Masculino , República da Coreia , Comportamento de Redução do Risco , Inquéritos e Questionários , Triglicerídeos/análise , Triglicerídeos/sangue
9.
Arterioscler Thromb Vasc Biol ; 40(8): 1830-1837, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32522007

RESUMO

OBJECTIVE: Adrenal gland secretes stress-induced glucocorticoids (iGCs) to coping with stress. Previous study showed that SR-BI (scavenger receptor BI) null (SR-BI-/-) mice failed to generate iGC in stress conditions, suggesting that SR-BI-mediated cholesterol uptake from HDL (high-density lipoprotein) is a key regulator for iGC production. However, the LDL (low-density lipoprotein)/LDLr (LDL receptor) pathway can also provide cholesterol for iGC synthesis, but rodents have limited LDL levels in circulation. Here, we generated SR-BI-/-ApoBtg (apolipoprotein B transgenic) mice with normal LDL levels in circulation to determine the relative contribution of the HDL/SR-BI and LDL/LDLr pathways to iGC production in stress conditions. Approach and Results: To obtain mouse models with normal LDL levels, SR-BI-/- mice were bred to ApoBtg mice. Then, the F1 SR-BI±ApoBtg mice were backcrossed to SR-BI-/- to obtain SR-BI-/-ApoBtg, SR-BI-/-ApoBwt (apolipoprotein B wild type), and SR-BI+/+ApoBtg mice. We first examined the lipoprotein profile, which shows a 6.5-fold increase in LDL levels in SR-BI-/-ApoBtg mice compared with SR-BI-/-ApoBwt mice. Then, we induced stress with adrenocorticotropic hormone and cecal ligation and puncture. One hour after adrenocorticotropic hormone stimulation, SR-BI+/+ApoBtg control mice produced iGC (14.9-fold), but both SR-BI-/-ApoBwt and SR-BI-/-ApoBtg showed no iGC production (P<0.001). Three hours after cecal ligation and puncture treatment, SR-BI+/+ApoBtg control mice showed iGC production (6.4-fold), but both SR-BI-/-ApoBwt and SR-BI-/-ApoBtg mice showed no iGC production (P<0.001). CONCLUSIONS: SR-BI-/-ApoBtg mice fail to produce iGC in stress conditions even though with restored LDL levels in circulation. These findings clarify that the HDL/SR-BI, not LDL/LDLr, pathway is responsible for iGC production in stress conditions.


Assuntos
Glucocorticoides/biossíntese , Receptores de LDL/fisiologia , Receptores Depuradores Classe B/fisiologia , Estresse Psicológico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Animais , Lipoproteínas LDL/sangue , Camundongos , Camundongos Endogâmicos C57BL
10.
Med Care ; 58 Suppl 6 Suppl 1: S31-S39, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32412951

RESUMO

BACKGROUND: Racial and ethnic minorities are disproportionately affected by diabetes and at greater risk of experiencing poor diabetes-related outcomes compared with non-Hispanic whites. The Affordable Care Act (ACA) was implemented to increase health insurance coverage and reduce health disparities. OBJECTIVE: Assess changes in diabetes-associated biomarkers [hemoglobin A1c (HbA1c) and low-density lipoprotein] 24 months pre-ACA to 24 months post-ACA Medicaid expansion by race/ethnicity and insurance group. RESEARCH DESIGN: Retrospective cohort study of community health center (CHC) patients. SUBJECTS: Patients aged 19-64 with diabetes living in 1 of 10 Medicaid expansion states with ≥1 CHC visit and ≥1 HbA1c measurement in both the pre-ACA and the post-ACA time periods (N=13,342). METHODS: Linear mixed effects and Cox regression modeled outcome measures. RESULTS: Overall, 33.5% of patients were non-Hispanic white, 51.2% Hispanic, and 15.3% non-Hispanic black. Newly insured Hispanics and non-Hispanic whites post-ACA exhibited modest reductions in HbA1c levels, similar benefit was not observed among non-Hispanic black patients. The largest reduction was among newly insured Hispanics versus newly insured non-Hispanic whites (P<0.05). For the subset of patients who had uncontrolled HbA1c (HbA1c≥9%) within 3 months of the ACA Medicaid expansion, non-Hispanic black patients who were newly insured gained the highest rate of controlled HbA1c (hazard ratio=2.27; 95% confidence interval, 1.10-4.66) relative to the continuously insured group. CONCLUSIONS: The impact of the ACA Medicaid expansion on health disparities is multifaceted and may differ across racial/ethnic groups. This study highlights the importance of CHCs for the health of minority populations.


Assuntos
Diabetes Mellitus/sangue , Disparidades nos Níveis de Saúde , Patient Protection and Affordable Care Act , Adolescente , Adulto , Afro-Americanos/estatística & dados numéricos , Biomarcadores/sangue , Criança , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Hemoglobina A Glicada/análise , Hispano-Americanos/estatística & dados numéricos , Humanos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Patient Protection and Affordable Care Act/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
11.
Nutr Metab Cardiovasc Dis ; 30(7): 1137-1146, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32456947

RESUMO

BACKGROUND AND AIMS: The increased risk of cardiovascular disease under hypercholesterolemia is due to associations between oxidized low-density lipoprotein (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) and between ox-LDL and coagulant profiles. We investigated the impact of different ox-LDL levels on coagulation time and plasma metabolomes in subjects with borderline hypercholesterolemia. METHODS AND RESULTS: One hundred thirty-one subjects with borderline hypercholesterolemia (serum cholesterol ≥200 mg/dL) were divided into low ox-LDL (n = 66) and high ox-LDL (n = 65) groups. After adjusting for confounding factors, the high ox-LDL group exhibited a significantly decreased activated partial thromboplastin time (aPTT) and prothrombin time (PT) and increased Lp-PLA2 activity. Compared to the low ox-LDL group, the high ox-LDL group exhibited significantly increased intensities of 17 lysophosphatidylcholines (lysoPCs) and 7 lysophosphatidylethanolamines (lysoPEs). Ox-LDL was inversely correlated with aPTT and PT and positively correlated with Lp-PLA2 activity. Positive correlations were also found among ox-LDL, Lp-PLA2 activity, lysoPCs, and lysoPEs. LysoPCs and lysoPEs were inversely correlated with PT and aPTT. The identified plasma metabolites, including amino acids, fatty acid amides, acylcarnitines, and lysophospholipids, were significantly upregulated in the high ox-LDL group. CONCLUSION: High ox-LDL levels may be involved in the development of a procoagulant state in subjects with borderline hypercholesterolemia by increasing Lp-PLA2 activity and lysoPC and lysoPE levels.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Fatores de Coagulação Sanguínea/análise , Coagulação Sanguínea , Hipercolesterolemia/sangue , Lipoproteínas LDL/sangue , Lisofosfatidilcolinas/sangue , Lisofosfolipídeos/sangue , Biomarcadores/sangue , Feminino , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/enzimologia , Masculino , Metabolômica , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Regulação para Cima
12.
Clín. investig. arterioscler. (Ed. impr.) ; 32(2): 49-58, mar.-abr. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-187146

RESUMO

Background and aims: The first line of therapy in children with hypercholesterolaemia is therapeutic lifestyle changes (TLSC). The efficacy of lifestyle intervention in children with familial hypercholesterolaemia (FH), where LDL-C levels are genetically driven, deserves a focused study. Aims: To evaluate the impact of a lifestyle education program, focused on food patterns and physical activity, on lipid profiles assessed by nuclear magnetic resonance (NMR) in children with FH vs. non-FH. Methods: Phase 1 was a cross-sectional study of baseline characteristics, and phase 2 was a prospective TLSC intervention study. In total, the study included 238 children (4 to 18 years old; 47% girls) attending the lipid unit of our hospital due to high cholesterol levels. Eighty-five were diagnosed with FH (72% genetic positive), and 153 were diagnosed with non-Familial hypercholesterolaemia. A quantitative food frequency questionnaire (FFQ) including 137 items was used. Physical activity (PA) was assessed by the Minnesota questionnaire. The lipid profile was assessed using the 2D-1H-NMR (Liposcale test). A total of 127 children (81 in the FH group) participated in the prospective phase and were re-assessed after 1 year of the TLSC intervention, consisting of education on lifestyle changes delivered by a specialized nutritionist. Results: The FH and non-FH groups were similar in anthropometry and clinical data, except that those in the FH were slightly younger than those in the non-FH group. Both the FH and non-FH groups showed a similar diet composition characterized by a high absolute calorie intake and a high percentage of fat, mainly saturated fat. The PA was below the recommended level in both groups. After one year of TLSC, the percentage of total and saturated fats was reduced, and the amount of fiber increased significantly in both groups. The percentage of protein increased slightly. The number of children engaged in at least 1 hour/day of PA increased by 56% in the FH group and by 53% in the non-FH group, and both these increases were significant. The total and small-LDL particle numbers were reduced in both groups, although the absolute change was greater in the FH group than in the non-FH group. Conclusions: Educational strategies to implement TLSC in children lead to empowerment, increased adherence, and overall metabolic improvement in children with high blood cholesterol, including those with FH


Antecedentes y objetivos: La primera línea de terapia en niños con hipercolesterolemia son los cambios terapéuticos en el estilo de vida (TLSC). La eficacia de la intervención en el estilo de vida en niños con hipercolesterolemia familiar (HF), en los que los niveles de LDL-C son generados genéticamente, merece un estudio específico. Objetivos: Evaluar el impacto de un programa de educación sobre el estilo de vida, centrado en los patrones alimentarios y la actividad física, sobre el perfil lipídico evaluado por resonancia magnética nuclear (RMN) en niños con HF versus no HF. Métodos: La fase 1 fue un estudio transversal de las características basales, y la fase 2 fue un estudio prospectivo de intervención mediante TLSC. En total, el estudio incluyó a 238 niños (de 4 a 18 años; 47% niñas) que asistieron a la unidad de lípidos de nuestro hospital debido a los altos niveles de colesterol. Ochenta y cinco fueron diagnosticados con HF (72% genéticamente positivos), y 153 fueron diagnosticados de no HF. Se utilizó un cuestionario cuantitativo de frecuencia de alimentos (FFQ) que incluye 137 ítems. La actividad física (AF) se evaluó mediante el cuestionario de Minnesota. El perfil lipídico se evaluó mediante la prueba 2D-1H-NMR (Liposcale Test). Un total de 127 niños (81 en el grupo HF) participaron en la fase prospectiva y fueron reevaluados después de 1 año de la intervención mediante TLSC, que consistió en educación sobre cambios en el estilo de vida impartida por una nutricionista especializada. Resultados: Los grupos HF y no HF fueron similares en los datos antropométricos y clínicos, excepto que los HF eran ligeramente más jóvenes que los no HF. Los participantes de ambos grupos mostraron una composición de dieta similar caracterizada por un alto consumo de calorías totales y un alto porcentaje de grasas, principalmente grasas saturadas. La AF estuvo por debajo del nivel recomendado en ambos grupos. Después de un año de TLSC, se redujo el porcentaje de grasas totales y saturadas, y la cantidad de fibra aumentó significativamente en ambos grupos. El porcentaje de proteína aumentó ligeramente. El número de niños involucrados en al menos 1 hora/día de AF aumentó en un 56% en el grupo de HF y en un 53% en el grupo sin HF, y ambos aumentos fueron significativos. Los números de partículas LDL totales y pequeñas se redujeron en ambos grupos, aunque el cambio absoluto fue mayor en el grupo HF que en el grupo no HF. Conclusiones: Las estrategias educativas para implementar TLSC en niños conducen al empoderamiento, al aumento de la adherencia y a la mejora metabólica general en niños con colesterol alto en sangre, incluidos aquellos con HF


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Hipercolesterolemia/sangue , Hipercolesterolemia/terapia , Estilo de Vida , Educação de Pacientes como Assunto , Lipoproteínas LDL/sangue , Dietoterapia , Terapia por Exercício , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/terapia , Ressonância Magnética Nuclear Biomolecular , Estudos Transversais , Estudos Prospectivos , Resultado do Tratamento
14.
PLoS One ; 15(4): e0231582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302327

RESUMO

Atherosclerosis, the predominant cause of death in well-resourced countries, may develop in the presence of plasma lipid levels within the normal range. Inflammation may contribute to lesion development in these individuals, but the underlying mechanisms are not well understood. Transgenic mice expressing α-def-1 released from activated neutrophils develop larger lipid and macrophage-rich lesions in the proximal aortae notwithstanding hypocholesterolemia caused by accelerated clearance of α-def-1/low-density lipoprotein (LDL) complexes from the plasma. The phenotype does not develop when the release of α-def-1 is prevented with colchicine. However, ApoE-/- mice crossed with α-def-1 mice or given exogenous α-def-1 develop smaller aortic lesions associated with reduced plasma cholesterol, suggesting a protective effect of accelerated LDL clearance. Experiments were performed to address this seeming paradox and to determine if α-def-1 might provide a means to lower cholesterol and thereby attenuate atherogenesis. We confirmed that exposing ApoE-/- mice to α-def-1 lowers total plasma cholesterol and decreases lesion size. However, lesion size was larger than in mice with total plasma cholesterol lowered to the same extent by inhibiting its adsorption or by ingesting a low-fat diet. Furthermore, α-def-1 levels correlated independently with lesion size in ApoE-/- mice. These studies show that α-def-1 has competing effects on atherogenesis. Although α-def-1 accelerates LDL clearance from plasma, it also stimulates deposition and retention of LDL in the vasculature, which may contribute to development of atherosclerosis in individuals with normal or even low plasma levels of cholesterol. Inhibiting α-def-1 may attenuate the impact of chronic inflammation on atherosclerotic vascular disease.


Assuntos
Aorta/patologia , Aterosclerose/patologia , Colesterol/sangue , alfa-Defensinas/metabolismo , Animais , Anticolesterolemiantes/administração & dosagem , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/metabolismo , Colesterol/metabolismo , Resina de Colestiramina/administração & dosagem , Colchicina/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Camundongos , Camundongos Knockout para ApoE , Camundongos Transgênicos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , alfa-Defensinas/genética
15.
Ecotoxicol Environ Saf ; 193: 110318, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32105945

RESUMO

The current study aimed to examine, for the first time, the relationship between exposure to deltamethrin (DLM) and atherogenic lipid profile disorders in adult Wistar rats, as well as, to verify the mechanism of the beneficial role of Zygophyllum album leaves extracts (ZALE). The experimental study was assessed using DLM (4 mg/kg b.w) either alone or co administered with ZALE (400 mg/kg b.w) orally for 90 days in rats. RP-HPLC-DAD-ESI-QTOF-MS was used to identify the bioactive metabolites present in ZALE. Plasmatic and aortic total cholesterol (TC), LDL-cholesterol (LDL-C), native LDL (LDL-apo B-100) and oxidized LDL (ox-LDL) were evaluated using auto-analyzer and a sandwich ELISA, respectively. The protein expressions of LDLR (native LDL receptor) and CD36 (Scavenger receptor class B) were evaluated in aorta or liver with a Western blot. The pathology has been confirmed with lipid stain (Oil Red O). Phytochemicals analysis revealed the presence of fifteen saponins in ZALE. Rats intoxicated with DLM revealed a significant increase in plasmatic and aortic lipid profile (TC, LDL-C, LDL-apo B-100 and ox-LDL), as well as, the concentration of the plasmatic cytokines include TNF-α, IL-2 and IL-6, compared to control. Hepatic native LDL and aortic CD36 receptor expression were increased in DLM treated group, however aortic LDL-R does not present any modification, when compared to control. The detected disturbances in lipid parameters were supported by Oil Red O applied. Due to their antioxidant activity, the bioactive compounds in ZALE as powerful agents able to prevent the pro-atherogenic effect observed in DLM-treated animals. These metabolites modulated most of inflammatory markers, prevented accumulation of lipid and lipoprotein biomarkers, regulated the major receptor regulators of hepatic cholesterol metabolism, as well as normalize lipid distribution in liver and aorta tissue.


Assuntos
Aorta/efeitos dos fármacos , Aterosclerose/prevenção & controle , Poluentes Ambientais/toxicidade , Lipoproteínas LDL/sangue , Nitrilos/toxicidade , Piretrinas/toxicidade , Saponinas/farmacologia , Zygophyllum/química , Animais , Aorta/imunologia , Aorta/metabolismo , Aterosclerose/imunologia , Aterosclerose/metabolismo , Antígenos CD36/metabolismo , Colesterol/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Masculino , Folhas de Planta/química , Ratos , Ratos Wistar , Receptores de LDL/metabolismo , Saponinas/isolamento & purificação , Fator de Necrose Tumoral alfa/metabolismo
16.
Zhonghua Er Ke Za Zhi ; 58(2): 101-106, 2020 Feb 02.
Artigo em Chinês | MEDLINE | ID: mdl-32102145

RESUMO

Objective: To analyze the genetic characteristics of a five generations pedigree with homozygous familial hypercholesterolemia (HoFH). Methods: Prospective study. Twenty family members included a proband diagnosed as familial hyperlipidemia at the cardiology Department of Xi'an Children's Hospital in October 2018 were research object. Clinical data were collected. Genome DNAs were extracted. Whole exons sequencing was performed on the proband using target capture next generation sequencing. Candidate gene mutation sites identified by bioinformatics were verified by Sanger sequencing in the family members. The genotype-phenotype correlation of the pedigree was analyzed between heterozygous mutation carriers and non-carriers. Results: The proband was a 7-years and 10-month-old boy. He was born with a roundgreen bean size yellow skin protuberance in the skin of the coccyx. Since the age of 3-4 years old, xanthoma-like lesions with a diameter of 0.5-1.5 cm gradually appeared in the skin of bilateral elbow joints, knee joints and Achilles tendon. The height, weight and intellectual development of the child were the same as those of normal children at the same age. No similar xanthoma-like lesion was found in the other family members. The proband's total cholesterol (TC) reached 18.16-21.24 mmol/L, and his low density lipoproteincholesterol (LDL-C) was 14.08-15.51 mmol/L. Carotid ultrasonography showed diffuse sclerotic plaques in bilateral carotid and vertebral arteries, and color Doppler echocardiography revealed aortic valve thickening and calcification. Gene testing identified that the proband carried a homozygous mutation C. 418G>A (p. E140K) in LDLR gene inherited from his parents who had a consanguineous marriage and carried a heterozygous mutation of LDLR-E140K, respectively.The TC, LDL-C and apolipoproteinB (ApoB) of LDLR-E140K gene heterozygous carriers ((8.40±0.13), (6.79±0.01) and (1.95±0.05) mmol/L, respectively) were significantly higher than those of non-carriers ((4.59±0.28), (3.35±0.39) and (0.86±0.10) mmol/L, t=7.269, 4.595, 6.311, respectively, P<0.05). Conclusions: LDLR-E140K gene homozygous mutation is first reported to be associated with most severe phenotype HoFH. The genotype-phenotype analysis of the pedigree shows that the clinical phenotype of the proband with homozygous mutation is the most serious, and all the heterozygous mutation carriers present with hypercholesterolemia phenotype. The investigation confirms that LDLR-E140K is the pathogenic variation of familial hyperlipidemia.


Assuntos
LDL-Colesterol/sangue , DNA/genética , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo I/genética , Receptores de LDL/genética , Valva Aórtica/diagnóstico por imagem , Sequência de Bases , Criança , Pré-Escolar , Análise Mutacional de DNA , Ecocardiografia Doppler , Feminino , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Hiperlipoproteinemia Tipo I/diagnóstico , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Lactente , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Proteínas de Membrana , Mutação , Linhagem , Fenótipo , Estudos Prospectivos
17.
Diabetes Res Clin Pract ; 161: 108036, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32006643

RESUMO

AIMS: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) level has been reported to be strongly associated with the pathogenesis of cardiovascular diseases. We focused on diabetic status and investigated its possible contribution to MDA-LDL level. METHODS: The study sample consisted of 2705 patients who were admitted to our hospital and underwent cardiac catheterization. Blood samples were obtained to measure the levels of fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, LDL, MDA-LDL and others. Body mass index (BMI) was also used in constructing structural equation modeling and Bayesian estimation. RESULTS: To explore the factors theoretically associated with MDA-LDL level, we performed structural equation modeling. We generated a path model that revealed that BMI, LDL level and FBS were significantly associated with MDA-LDL level (P < 0.001 for each factor), whereas insulin level and HbA1c level were not significantly associated (P = NS for both factors). Noted above was clearly demonstrated on the image of 2-D contour line by Bayesian structure equation modeling. CONCLUSIONS: This study clearly showed that hyperglycemia affects MDA-LDL level. An interaction between diabetes and dyslipidemia was shown in terms of activation of lipid oxidation.


Assuntos
Doenças Cardiovasculares/sangue , Complicações do Diabetes/sangue , Diabetes Mellitus/sangue , Hiperglicemia/sangue , Lipoproteínas LDL/sangue , Malondialdeído/sangue , Idoso , Teorema de Bayes , Índice de Massa Corporal , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/sangue , Dislipidemias/epidemiologia , Feminino , Humanos , Hiperglicemia/complicações , Hiperglicemia/epidemiologia , Insulina/sangue , Análise de Classes Latentes , Masculino , Malondialdeído/química , Pessoa de Meia-Idade
18.
Life Sci ; 243: 117246, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31904367

RESUMO

AIMS: Obesity induce low-grade inflammation and elicit insulin resistance (IR), exercise training accompanied by a low-fat diet has been prescribed as part of the treatment for managing obesity and IR. The purpose of this study is to evaluate the effect of eccentric exercise accompanied by a low-fat diet on glycolipid metabolism, exercise capacity, and macrophage polarization in obesity-induced IR mice. MATERIALS AND METHODS: Mice were fed with 60% high fat diet (HFD) for 12 weeks and subsequently treated with eccentric exercise or/and dietary restriction for 8 weeks. Related biochemical index were examined both before and during intervention to evaluate the ability of glycolipid metabolism. Exercise capacity was measured to verify the results of biochemical index. At 12 weeks and 12 + 8 weeks, infiltration was observed by H&E staining in adipose tissue, and macrophage polarization was detected by Immunofluorescence staining and ELISA. KEY FINDING: 1) obesity-induced IR model was established by HFD fed for 12 weeks accompanied by impaired exercise ability and increased M1 macrophage, 2) eccentric exercise accompanied by a low-fat diet markedly rescued obesity-induced IR and improved exercise capacity, 3) eccentric exercise accompanied by a low-fat diet markedly inhibited M1 macrophage polarization and activated M2 macrophage. SIGNIFICANCE: Eccentric exercise accompanied by a low-fat diet rescued obesity-induced IR and improved exercise capacity, which were associated with the inhibition of M1 macrophage polarization and the activation of M2 macrophage. These indicate that macrophage polarization provides the potential target of intervention for inflammation and IR in obesity.


Assuntos
Dieta Hiperlipídica , Macrófagos/citologia , Obesidade/etiologia , Condicionamento Físico Animal/fisiologia , Animais , Hipercolesterolemia/prevenção & controle , Resistência à Insulina , Lipoproteínas LDL/sangue , Ativação de Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
19.
Lipids ; 55(1): 63-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31944322

RESUMO

Palmitoleic acid has been classified as an insulin-sensitizing lipokine, but evidence for this from human studies has been inconsistent. We hypothesized that this is related to either the types of samples or conditions under which samples are collected. We measured plasma palmitoleic acid and total free fatty acids (FFA) using ultra-performance liquid chromatography in blood samples collected from 34 adults under a variety of conditions. We collected duplicate samples of adipose (n = 10), FFA (n = 9), and very low density lipoprotein triacylglycerol (VLDL-TAG) (n = 7) to measure the palmitoleic acid as a percentage of total fatty acids. We tested whether the percentage of palmitoleic acid was correlated with insulin resistance, as measured by homeostatic model of insulin resistance (HOMA-IR). Adipose stearoyl-coenzyme A desaturase 1 (SCD-1) protein was measured by capillary Western blotting. FFA-palmitoleic acid percentage increased as a function of total FFA and was greater (p < 0.005) in females than males. Adipose palmitoleic acid percentage was greater in females than males (p < 0.001), as was adipose SCD-1. Palmitoleic acid was greater in femoral fat than in abdominal fat in both females and males (p < 0.001), and correlated positively with HOMA-IR only in females. The test-retest reliability values for percentage palmitoleic acid were 7 ± 10% for adipose, 24 ± 26% for VLDL, and 53 ± 31% for FFA. Because FFA-palmitoleic acid percentage varies as a function of total FFA, investigators should re-evaluate how palmitoleic acid data is presented. The positive relationship between adipose palmitoleic acid and HOMA-IR in females suggests that it is not a potent insulin-sensitizing lipokine in humans.


Assuntos
Ácidos Graxos Monoinsaturados/sangue , Ácidos Graxos não Esterificados/sangue , Lipoproteínas LDL/sangue , Obesidade/metabolismo , Estearoil-CoA Dessaturase/metabolismo , Triglicerídeos/sangue , Absorciometria de Fóton , Tecido Adiposo/química , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Resistência à Insulina , Masculino , Obesidade/sangue , Estudos Prospectivos , Caracteres Sexuais , Adulto Jovem
20.
Nanotoxicology ; 14(3): 355-371, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31909645

RESUMO

The use of indium oxide (In2O3) and indium-metal hybrids for various applications, including the manufacture of batteries and liquid crystal displays, increases the chances of human exposure to In2O3 via inhalation, especially in occupational settings. However, there is little information available on the toxic effects of In2O3 nanoparticles (NPs) on secondary organs following pulmonary exposure. In this study, we evaluated the effect of In2O3 NPs on atherosclerotic plaque formation and the related mechanisms after pulmonary exposure in low-density lipoprotein receptor knockout (Ldlr-/-) mice. At 10 weeks after a single pharyngeal aspiration, In2O3 NPs caused chronic active inflammation, pulmonary alveolar proteinosis, and accumulation of inflammatory cells in the peribronchial and perivascular areas of the lungs. The expression of pro-inflammatory cytokines in the lung tissue, including TNF-α and MCP-1, was markedly increased by treatment with In2O3 NPs. In the In2O3 NP-treated groups, the levels of total cholesterol and low-density lipoprotein in the plasma were increased, whereas HDL cholesterol showed no significant changes compared to vehicle control. The formation of atherosclerotic lesions was increased by treatment with In2O3 NPs. Real-time PCR analysis of the aorta showed that IL-6 and MCP-1 expression was up-regulated upon treatment with In2O3 NPs. These results suggested that the pulmonary inflammation induced by In2O3 NPs aggravates the progression of atherosclerotic plaque formation, possibly by the alteration of the plasma lipid profile and enhancement of the aortic inflammatory processes.


Assuntos
Aterosclerose/induzido quimicamente , Índio/toxicidade , Nanopartículas/toxicidade , Placa Aterosclerótica/induzido quimicamente , Pneumonia/induzido quimicamente , Receptores de LDL/metabolismo , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , Citocinas/metabolismo , Índio/química , Exposição por Inalação , Lipoproteínas LDL/sangue , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Knockout , Nanopartículas/química , Placa Aterosclerótica/sangue , Placa Aterosclerótica/metabolismo , Pneumonia/sangue , Pneumonia/metabolismo , Receptores de LDL/genética
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