RESUMEN
Obesity is an important risk factor for the development of pregnancy complications. We investigated the effects of pregestational overweight and obesity on maternal lipidome during pregnancy and on newborns' characteristics. The study encompassed 131 pregnant women, 99 with pre-pregnancy body mass index (BMI) < 25 kg/m2 and 32 with BMI ≥ 25 kg/m2. Maternal lipid status parameters, plasma markers of cholesterol synthesis and absorption and sphingolipids were determined in each trimester. Data on neonatal height, weight and APGAR scores were assessed. The results showed a higher prevalence (p < 0.05) of pregnancy and childbirth complications among the participants with elevated pregestational BMI. Levels of total cholesterol, HDL-cholesterol (p < 0.05) and LDL-cholesterol (p < 0.01) were significantly lower, and concentrations of triglycerides were higher (p < 0.05) in women with increased pre-gestational BMI. Lower concentrations of the cholesterol synthesis marker, desmosterol, in the 2nd trimester (p < 0.01) and the cholesterol absorption marker, campesterol, in each trimester (p < 0.01, p < 0.05, p < 0.01, respectively) were also found in this group. Markers of maternal cholesterol synthesis were in positive correlation with neonatal APGAR scores in the group of mothers with healthy pre-pregnancy weight but in negative correlation in the overweight/obese group. Our results indicate that gestational adaptations of maternal lipidome depend on her pregestational nutritional status and that such changes may affect neonatal outcomes.
Asunto(s)
Índice de Masa Corporal , Lipidómica , Obesidad , Sobrepeso , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Recién Nacido , Adulto , Obesidad/metabolismo , Obesidad/sangre , Lipidómica/métodos , Sobrepeso/metabolismo , Complicaciones del Embarazo/metabolismo , Complicaciones del Embarazo/sangre , Lípidos/sangre , Colesterol/sangreRESUMEN
The aim of this multicentric study was to assess the impacts of oxidative stress, inflammation, and the presence of small, dense, low-density lipoproteins (sdLDL) on the antioxidative function of high-density lipoprotein (HDL) subclasses and the distribution of paraoxonase-1 (PON1) activity within HDL in patients with ST-segment elevation acute myocardial infarction (STEMI). In 69 STEMI patients and 67 healthy control subjects, the lipoproteins' subclasses were separated using polyacrylamide gradient (3-31%) gel electrophoresis. The relative proportion of sdLDL and each HDL subclass was evaluated by measuring the areas under the peaks of densitometric scans. The distribution of the relative proportion of PON1 activity within the HDL subclasses (pPON1 within HDL) was estimated using the zymogram method. The STEMI patients had significantly lower proportions of HDL2a and HDL3a subclasses (p = 0.001 and p < 0.001, respectively) and lower pPON1 within HDL3b (p = 0.006), as well as higher proportions of HDL3b and HDL3c subclasses (p = 0.013 and p < 0.001, respectively) and higher pPON1 within HDL2 than the controls. Independent positive associations between sdLDL and pPON1 within HDL3a and between malondialdehyde (MDA) and pPON1 within HDL2b were shown in the STEMI group. The increased oxidative stress and increased proportion of sdLDL in STEMI are closely related to the compromised antioxidative function of small HDL3 particles and the altered pPON1 within HDL.
Asunto(s)
Lipoproteínas HDL , Infarto del Miocardio con Elevación del ST , Humanos , Arildialquilfosfatasa , Lipoproteínas , Lipoproteínas LDLRESUMEN
A specific feature of dyslipidemia in pregnancy is increased high-density lipoprotein (HDL) cholesterol concentration, which is probably associated with maternal endothelium protection. However, preeclampsia is most often associated with low HDL cholesterol, and the mechanisms behind this change are scarcely explored. We aimed to investigate changes in HDL metabolism in risky pregnancies and those complicated by late-onset preeclampsia. We analyze cholesterol synthesis (cholesterol precursors: desmosterol, 7-dehydrocholesterol, and lathosterol) and absorption markers (phytosterols: campesterol and ß-sitosterol) within HDL particles (NCSHDL), the activities of principal modulators of HDL cholesterol's content, and major HDL functional proteins levels in mid and late pregnancy. On the basis of the pregnancy outcome, participants were classified into the risk group (RG) (70 women) and the preeclampsia group (PG) (20 women). HDL cholesterol was lower in PG in the second trimester compared to RG (p < 0.05) and followed by lower levels of cholesterol absorption markers (p < 0.001 for campesterolHDL and p < 0.05 for ß-sitosterolHDL). Lowering of HDL cholesterol between trimesters in RG (p < 0.05) was accompanied by a decrease in HDL phytosterol content (p < 0.001), apolipoprotein A-I (apoA-I) concentration (p < 0.05), and paraoxonase 1 (PON1) (p < 0.001), lecithin-cholesterol acyltransferase (LCAT) (p < 0.05), and cholesterol ester transfer protein (CETP) activities (p < 0.05). These longitudinal changes were absent in PG. Development of late-onset preeclampsia is preceded by the appearance of lower HDL cholesterol and NCSHDL in the second trimester. We propose that reduced capacity for intestinal HDL synthesis, decreased LCAT activity, and impaired capacity for HDL-mediated cholesterol efflux could be the contributing mechanisms resulting in lower HDL cholesterol.
Asunto(s)
Preeclampsia , Humanos , Femenino , Embarazo , HDL-Colesterol/metabolismo , Colesterol/metabolismo , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , Transporte Biológico , Apolipoproteína A-I/metabolismo , Arildialquilfosfatasa/metabolismoRESUMEN
Polycystic ovary syndrome (PCOS) is associated with altered lipid profile and increased small, dense LDL particles (sdLDL). Considering that paraoxonase 1 (PON1) is an antioxidative enzyme located on HDL particles, the aim of this study was to investigate the connection between oxidative stress (OS) and PON1 activity with lipoprotein subclasses in PCOS depending on obesity. In 115 PCOS patients, lipoprotein subclasses distributions were determined by gradient gel electrophoresis. OS status was assessed by total oxidative status (TOS), advanced oxidation protein products, malondialdehyde (MDA), prooxidant-antioxidant balance (PAB), total antioxidative status (TAS) and superoxide dismutase (SOD) and PON1 activity. Overweight/obese PCOS patients (n 55) had increased OS compared with normal weight patients (n 60). In addition, overweight/obese group had lower HDL size and higher proportion of HDL 3a subclasses (P < 0·05). PAB was in negative correlation with HDL 2a (P < 0·001), whereas MDA and SOD correlated positively with HDL 3 subclasses (P < 0·05). Serum PON1 activity was positively associated with proportions of PON1 activity on HDL 2b (P < 0·05) and 2a (P < 0·01), but negatively with the proportion on HDL 3 particles (P < 0·01). LDL B phenotype patients had increased TAS, SOD and PON1 activity on HDL 2b, but decreased PON1 activity on HDL 3 subclasses. OS is associated with altered lipoprotein subclasses distribution in PCOS patients. Obesity in PCOS affects the profile of HDL subclasses, reflected through the reduced proportion of PON1 activity on HDL 3 subclasses in the presence of sdLDL particles.
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Dislipidemias , Síndrome del Ovario Poliquístico , Humanos , Femenino , Sobrepeso , Lipoproteínas HDL3/metabolismo , Estrés Oxidativo , Antioxidantes/metabolismo , Inflamación , Obesidad , Superóxido Dismutasa/metabolismo , Arildialquilfosfatasa/metabolismoRESUMEN
OBJECTIVES: Obstructive sleep apnea (OSA) is a common condition closely related to obesity, insulin resistance, dyslipidemia, and cardiovascular disease. The aim of this study was to explore the possible relationship between OSA and proprotein convertase subtilisin/kexin type 9 (PCSK9). METHODS: Full-night polysomnography was performed on 150 participants who were divided into three groups: controls, OSA patients on statin therapy, and OSA patients not on statin therapy. Biochemical markers, plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, and PCSK9 were determined. RESULTS: PCSK9 was highest in OSA patients on statins compared to the control group and to OSA patients not on statins (p = 0.036 and p = 0.039, respectively), after adjustment for body mass index (BMI). LDL diameter was greater in OSA patients not on statins compared to OSA patients on statins (p = 0.032). PCSK9 was highest in the group of patients with all three risk factors (diagnosed OSA, statins, BMI ≥25 kg/m2) compared to groups with no, one, and two risk factors (p = 0.031, p = 0.001, and p = 0.029, respectively). Presence of OSA, statin therapy, and BMI ≥25 kg/m2 when combined were independently associated with higher levels of PCSK9 when adjusted for antihypertensive therapy, small dense LDL, and HDL 3c subclass (odds ratio = 2.849; interquartile range [1.026-7.912], p = 0.044). CONCLUSION: Statin therapy was closely related to PCSK9. OSA along with obesity and statin use induces elevation of PCSK9.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Obesidad , Proproteína Convertasa 9 , Apnea Obstructiva del Sueño , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Obesidad/complicaciones , Proproteína Convertasa 9/sangre , Apnea Obstructiva del Sueño/complicacionesRESUMEN
Atherosclerosis is responsible for large cardiovascular mortality in many countries globally. It has been shown over the last decades that the reduction of atherosclerotic progression is a critical factor for preventing future cardiovascular events. Low-density lipoproteins (LDL) have been successfully targeted, and their reduction is one of the key preventing measures in patients with atherosclerotic disease. LDL particles are pivotal for the formation and progression of atherosclerotic plaques; yet, they are quite heterogeneous, and smaller, denser LDL species are the most atherogenic. These particles have greater arterial entry and retention, higher susceptibility to oxidation, as well as reduced affinity for the LDL receptor. Increased proportion of small, dense LDL particles is an integral part of the atherogenic lipoprotein phenotype, the most common form of dyslipidemia associated with insulin resistance. Recent data suggest that both genetic and epigenetic factors might induce expression of this specific lipid pattern. In addition, a typical finding of increased small, dense LDL particles was confirmed in different categories of patients with elevated cardiovascular risk. Small, dense LDL is an independent risk factor for cardiovascular diseases, which emphasizes the clinical importance of both the quality and the quantity of LDL. An effective management of atherosclerotic disease should take into account the presence of small, dense LDL in order to prevent cardiovascular complications.
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Aterosclerosis , Dislipidemias , Resistencia a la Insulina , Humanos , Lipoproteínas LDL , Factores de RiesgoRESUMEN
Background and Objectives: Diabetic foot (DF) development is driven by complex interactions of hyperglycemia, inflammation, and oxidative stress (OS). We aimed to investigate OS and inflammatory biomarkers in patients with DF and their potential to improve early diagnosis and management of DF. Materials and Methods: The prooxidant−antioxidant balance (PAB), superoxide dismutase (SOD), total oxidative status (TOS), total sulfhydryl groups (SHG), routine biochemical parameters, and complete blood count were determined in 42 patients with type-2 DM, of which 23 patients had DF, while 19 patients were without DF complications. The neutrophils-to-lymphocyte ratio (NLR) was evaluated as a biomarker of inflammation. Results: Patients with DF had significantly higher (p < 0.05) PAB levels (170 ± 33.9 U/L) compared to those without DF complications (142 ± 31.3 U/L). In addition, patients with DF had significantly reduced SOD activities (p < 0.01). NLR values were significantly higher in the DF group (median: 2.8; interquartile range: 2.0−4.3) than in the group without DF (median: 1.4; interquartile range: 1.4−2.1; p < 0.01). A positive correlation was found between the PAB and NLR index (r = 0.449; p < 0.05). The diagnostic accuracy of both PAB (AUC = 0.741; p < 0.01) and NLR (AUC = 0.760; p < 0.01) was estimated as acceptable. Conclusions: In conclusion, the development of DF is associated with enhanced OS and inflammation processes. PAB and NLR could be useful non-invasive biomarkers of DF development.
Asunto(s)
Diabetes Mellitus , Pie Diabético , Humanos , Estrés Oxidativo , Antioxidantes/metabolismo , Biomarcadores , Especies Reactivas de Oxígeno , Inflamación/complicaciones , Neutrófilos/metabolismo , Superóxido DismutasaRESUMEN
Resistin might be involved with general inflammation and endothelial dysfunction observed in preeclampsia. We aimed to investigate longitudinal changes in resistin concentrations during high-risk pregnancies and evaluate their significance in preeclampsia development. Ninety-one patients were recruited at 11-14 weeks of gestation. They were followed towards the end of each trimester and before their deliveries. Of the 91 pregnant women, 21 developed preeclampsia, while 70 women did not develop preeclampsia despite being at risk. Compared to the 1st trimester, resistin concentration significantly increased during the 2nd trimester (p<.001). When women were divided into groups of those who developed preeclampsia and those who did not develop preeclampsia, we noticed a significant difference only in women who did not develop preeclampsia (p<.001). Moreover, resistin concentration in the 1st trimester was statistically higher in women who developed preeclampsia when compared to those who did not develop preeclampsia (p<.001). The analysis of the Receiver Operating Characteristics (ROC) curves indicated that inclusion of triglycerides (TG), high-sensitivity C-reactive protein (CRP), and resistin (AUC = 0.870) improved diagnostic accuracy of the basic model including demographic and clinical parameters (AUC = 0.777) for preeclampsia prediction (p<.05). If the concentration of resistin is high in the 1st trimester, such pregnancy at risk is likely to develop preeclampsia as a complication, indicating that resistin concentration in the 1st trimester might contribute to existing predictive and prognostic models for preeclampsia. A multi-marker model, possibly including also resistin and other clinical, metabolic, and inflammatory parameters, seems to be the best approach in late-onset preeclampsia prediction.
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Preeclampsia/sangre , Preeclampsia/diagnóstico , Resistina/sangre , Adulto , Femenino , Humanos , Modelos Logísticos , Embarazo , Curva ROC , Factores de RiesgoRESUMEN
Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical studies, glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be a promising strategy in reducing the incidence of CRC in patients with diabetes. However, available findings are inconclusive, and further studies are required. In this review, novel evidence on molecular mechanisms linking T2DM with CRC development, progression, and survival will be discussed. In addition, the potential role of GLP-1RAs therapies in CRC prevention will also be evaluated.
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Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hiperglucemia/epidemiología , Hipoglucemiantes/uso terapéutico , Comorbilidad , Humanos , Incidencia , Resistencia a la Insulina , Lipoproteínas LDL , Estrés OxidativoRESUMEN
Colorectal cancer (CRC) is a highly prevalent malignancy with multifactorial etiology, which includes metabolic alterations as contributors to disease development. Studies have shown that lipid status disorders are involved in colorectal carcinogenesis. In line with this, previous studies have also suggested that the serum high-density lipoprotein cholesterol (HDL-C) level decreases in patients with CRC, but more recently, the focus of investigations has shifted toward the exploration of qualitative properties of HDL in this malignancy. Herein, a comprehensive overview of available evidences regarding the putative role of HDL in CRC will be presented. We will analyze existing findings regarding alterations of HDL-C levels but also HDL particle structure and distribution in CRC. In addition, changes in HDL functionality in this malignancy will be discussed. Moreover, we will focus on the genetic regulation of HDL metabolism, as well as the involvement of HDL in disturbances of cholesterol trafficking in CRC. Finally, possible therapeutic implications related to HDL will be presented. Given the available evidence, future studies are needed to resolve all raised issues concerning the suggested protective role of HDL in CRC, its presumed function as a biomarker, and eventual therapeutic approaches based on HDL.
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Neoplasias Colorrectales/metabolismo , Lipoproteínas HDL/metabolismo , Animales , Apolipoproteína A-I/metabolismo , Apolipoproteínas M/metabolismo , Arildialquilfosfatasa/metabolismo , Biomarcadores/metabolismo , Carcinogénesis , Colesterol/metabolismo , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , HDL-Colesterol/metabolismo , Homeostasis , Humanos , Ratones , Polimorfismo de Nucleótido Simple , Medicina de Precisión , Receptores Depuradores de Clase B/metabolismoRESUMEN
Heparin-binding EGF-like growth factor (HB-EGF) is involved in atherosclerosis progression. We investigated association between plasma HB-EGF levels and lipid, oxidative stress and inflammatory biomarkers in pediatric patients with type 1 diabetes mellitus (T1DM). Levels of HB-EGF, high-sensitive C-reactive protein (hsCRP), prooxidant-antioxidant balance (PAB), total antioxidant status (TAS), oxidized low-density lipoproteins (oxLDL), metabolic control and serum lipid parameters and paraoxonase 1 (PON1) activity were determined in 74 patients and 40 controls. In comparison to controls, patients had significantly higher levels (p < 0.01) of HB-EGF, hsCRP, PAB and oxLDL particles (p < 0.001), but lower levels of TAS and PON1 activity. In T1DM group, HB-EFG levels were positively associated with hsCRP, PAB and oxLDL levels. hsCRP and oxLDL levels were independent predictors of HB-EGF concentration. We demonstrated that oxidative modifications of LDL particles and low-grade inflammation are main determinants of increased plasma HB-EGF levels, which indicates an interactive role of oxidative stress, dyslipidemia and inflammation.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Factor de Crecimiento Similar a EGF de Unión a Heparina/sangre , Adolescente , Arildialquilfosfatasa/sangre , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Niño , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Humanos , Lipoproteínas LDL/sangre , Masculino , Estrés OxidativoRESUMEN
BACKGROUND: Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. METHODS: The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. RESULTS: In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and ß-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). CONCLUSIONS: The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/ß-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.
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Enfermedades Cardiovasculares/patología , Colesterol/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Esteroles/metabolismo , Adulto , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Recent in vitro experiments have indicated that human resistin increases the number of lipoprotein particles secreted by the human hepatocytes and also influences their quality, in terms of generating more proatherogenic lipid particles. The aim of this study is to investigate associations of plasma resistin and peripheral blood mononuclear cells (PBMCs) resistin messenger RNA (mRNA) levels with different prevalence of small, dense low-density lipoprotein particles (sdLDL) in patients with indications for coronary angiography. This study included 65 patients requiring coronary angiography. There were 41 patients without significant stenosis and 24 patients with significant stenosis in at least one major coronary artery. Circulating resistin was measured by enzyme-linked immunosorbent assay; PBMC resistin mRNA was determined by real-time polymerase chain reaction. The LDL and high density lipoprotein subclasses were determined by gradient gel electrophoresis. Plasma resistin (P = 0.031) and PBMCs resistin mRNA (P = 0.004) were significantly higher in patients with proportion of sdLDL particles ≥ 50%, compared to the group with relative proportion of sdLDL particles < 50%. Plasma resistin correlated positively with creatinine (r = 0.456, P < 0.001) and resistin mRNA (r = 0.298, P = 0.014) but negatively with body mass index (r = -0.254, P = 0.034) and total cholesterol (r = -0.286, P = 0.021). Multiple linear regression analysis revealed LDL particle diameter as the only independent predictor of resistin mRNA (R(2) = 0.258; adjR(2) = 0.190). A significant association between resistin, both PBMCs mRNA and plasma protein, and the relative proportion of sdLDL particles in the circulation of coronary artery disease patients has been established, which implies that increased gene expression of resistin in PBMCs and higher resistin concentration in plasma are related to pro-atherogenic LDL particle phenotype.
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LDL-Colesterol/sangre , LDL-Colesterol/química , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Leucocitos Mononucleares/metabolismo , Resistina/sangre , Resistina/genética , Adulto , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Obesity-related childhood hypertension is associated with disturbances of serum lipids, but less is known about distribution of lipoprotein subclasses and activities of proteins involved in reverse cholesterol transport in hypertensive obese children. Our objective was to determine low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses distribution and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in hypertensive and non-hypertensive obese children. METHODS: A total of 40 hypertensive and 25 non-hypertensive obese children were enrolled. Lipoprotein subclasses were assessed by polyacrylamide gradient gel electrophoresis. LCAT and CETP activities were determined as a rate of formation and a rate of transfer of cholesteryl esters. RESULTS: Despite of comparable values of serum lipid parameters, a shift toward smaller LDL and HDL subclasses was observed in hypertensive compared to normotensive obese children. Activities of LCAT were similar, but proatherogenic CETP activities were significantly higher in the hypertensive group (p = 0.036). LCAT/net CETP ratio inversely correlated with relative proportion of small, dense LDL particles (ρ = -0.423; p = 0.025) in the group with hypertension. CONCLUSIONS: The results of our study demonstrated a tendency toward altered distribution of lipoprotein subclasses in favor of more proatherogenic particles in childhood hypertension. Also, hypertensive obese children had increased proatherogenic CETP activity.
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Hipertensión/sangre , Obesidad Infantil/sangre , Adolescente , Biomarcadores/sangre , Niño , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Femenino , Humanos , Hipertensión/diagnóstico , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Obesidad Infantil/diagnóstico , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Adulto JovenRESUMEN
BACKGROUND: Dyslipidemia is a common feature of chronic kidney disease (CKD). Although it has been observed that the pattern of lipid abnormalities can vary according to the stage of CKD, there is lack of data concerning the distribution of lipoprotein subclasses at various stages of the disease. In addition, association of proatherogenic small, dense low-density lipoprotein (sdLDL) subclasses with markers of inflammation, such is galectin-3, is not sufficiently explored. The aim of this study was to analyze concentrations and relative proportions of sdLDL-cholesterol (sdLDL-C) and galectin-3 in patients with CKD, with respect to the stage of the disease. Also, we sought possible independent associations of galectin-3 and sdLDL-C. METHODS: The study involved 100 hemodialysis (HD) and 50 pre-dialysis patients, together with 94 healthy individuals. SdLDL-C was measured by heparin-magnesium precipitation method. Galectin-3 was measured by ELISA technique. RESULTS: Galectin-3 levels were higher in pre-dialysis and HD patients than in the control group (p < 0.01). The concentration of sdLDL-C was highest in the pre-dialysis group and lowest in HD patients (p < 0.01). CKD patients with increased galectin-3 concentrations had significantly higher relative proportions of cholesterol in sdLDL (% sdLDL-C) than their counterparts with lower galectin-3 levels (p < 0.05). Relative proportion of sdLDL-C was shown to be an independent determinant of galectin-3 concentration. CONCLUSIONS: Our results demonstrated alterations in concentrations and proportions of sdLDL-C according to the stages of CKD. The observed independent associations of % sdLDL-C and galectin-3 provide further insight into their complex interaction during the progression of atherosclerosis in CKD.
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LDL-Colesterol/sangre , Galectina 3/sangre , Insuficiencia Renal Crónica/diagnóstico , Aterosclerosis/sangre , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal , Insuficiencia Renal Crónica/sangreRESUMEN
Childhood obesity with its growing prevalence worldwide presents one of the most important health challenges nowadays. Multiple mechanisms are involved in the development of this condition, as well as in its associations with various cardiometabolic complications, such as insulin resistance, diabetes, metabolic dysfunction-associated steatotic liver disease and cardiovascular diseases. Recent findings suggest that childhood obesity and associated dyslipidemia at least partly originate from epigenetic modifications that take place in the earliest periods of life, namely prenatal and perinatal periods. Hence, alterations of maternal metabolism could be fundamentally responsible for fetal and neonatal metabolic programming and consequently, for metabolic health of offspring in later life. In this paper, we will review recent findings on the associations among intrauterine and early postnatal exposure to undesirable modulators of metabolism, development of childhood obesity and later cardiometabolic complications. Special attention will be given to maternal dyslipidemia as a driven force for undesirable epigenetic modulations in offspring. In addition, newly proposed lipid biomarkers of increased cardiometabolic risk in obese children and adolescents will be analyzed, with respect to their predictive potential and clinical applicability.
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Dislipidemias , Obesidad Infantil , Humanos , Dislipidemias/metabolismo , Dislipidemias/etiología , Obesidad Infantil/complicaciones , Obesidad Infantil/metabolismo , Embarazo , Femenino , Efectos Tardíos de la Exposición Prenatal/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/metabolismo , Epigénesis Genética , Niño , Factores de Riesgo Cardiometabólico , Factores de Riesgo , Obesidad/complicaciones , Obesidad/metabolismoRESUMEN
PURPOSE: End-stage renal disease patients on chronic hemodialysis (HD) have a shortened life expectancy compared to the general population. The aim of this study was to evaluate a possible link between three new and emerging factors in renal pathophysiology: Klotho protein, telomere length in peripheral blood mononuclear cells (TL) and redox status parameters before HD (bHD) and after HD (aHD), and to test mortality prediction capability of these emerging parameters in a population of HD patients. METHODS: The study included 130 adult patients with average age 66 (54-72), on HD (3 times per week; 4-5 h per session). Klotho level, TL, routine laboratory parameters, dialysis adequacy and redox status parameters: advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), superoxide anion (O2.-), malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl group content (SHG), and superoxide dismutase (SOD) were determined. RESULTS: Klotho concentration was significantly higher aHD; 68.2 (22.6-152.9) vs. bHD 64.2 (25.5-119.8) (p = 0.027). The observed increase in TL was not statistically significant. AOPP, PAB, SHG, and SOD activity were significantly increased aHD (p > 0.001). The patients with the highest mortality risk score (MRS) had significantly higher PAB bHD (p = 0.002). Significantly lower O2.- (p < 0.001), SHG content (p = 0.072), and IMA (p = 0.002) aHD were found in patients with the lowest MRS values. Principal component analysis revealed redox balance-Klotho factor as a significant predictor of high mortality risk (p = 0.014). CONCLUSION: Decreased Klotho and TL attrition as well as redox status disturbance could be connected with higher mortality rate in HD patients.
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Antioxidantes , Fallo Renal Crónico , Adulto , Humanos , Anciano , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno , Estrés Oxidativo , Biomarcadores , Productos Avanzados de Oxidación de Proteínas/metabolismo , Leucocitos Mononucleares/química , Leucocitos Mononucleares/metabolismo , Albúmina Sérica/metabolismo , Diálisis Renal , Superóxido DismutasaRESUMEN
Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P < 0.001), due to reduction in relative proportion of LDL I (P < 0.01) and increase of LDL II (P < 0.001) and IIIA (P < 0.05) subclasses. In the same time, HDL size and proportions of HDL 2a particles significantly decreased (P < 0.001), with concomitant increase of HDL 3b and 3c subclasses (P < 0.05). Observed alterations were associated with changes in serum triglyceride levels. Rearrangement in LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.
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Peso al Nacer , Estatura , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Embarazo/sangre , Triglicéridos/sangre , Adulto , Cefalometría , Electroforesis , Femenino , Humanos , Estudios Longitudinales , Análisis Multivariante , Paridad , Tamaño de la Partícula , Periodo Posparto , Trimestres del Embarazo , Factores de Riesgo , Serbia , Factores SocioeconómicosRESUMEN
PURPOSE OF REVIEW: Obesity is accompanied by atherogenic dyslipidemia, a specific lipid disorder characterized by both quantitative and qualitative changes of plasma lipoproteins. The main alterations in the lipid profile include hypertriglyceridemia, reduced high-density lipoprotein (HDL) cholesterol level, and elevated small dense low-density lipoprotein (LDL) particles. Epidemiological data show that obesity is more common in women and is a frequent risk factor for reproductive disorders, metabolic complications in pregnancy, and cardiometabolic disease later in life. The aim of this narrative review is to discuss recent advances in the research of dyslipidemia in obesity, with an emphasis on female-specific disorders and cardiometabolic risk. RECENT FINDINGS: The focus of current research on dyslipidemia in obesity is moving toward structurally and functionally modified plasma lipoproteins. Special attention is paid to the pro-atherogenic role of triglyceride-rich lipoproteins and their remnants. Introduction of advanced analytical techniques enabled identification of novel lipid biomarkers with potential clinical applications. In particular, proteomic and lipidomic studies have provided significant progress in the comprehensive research of HDL's alterations in obesity. Obesity-related dyslipidemia is a widespread metabolic disturbance in polycystic ovary syndrome patients and high-risk pregnancies, but is seldom evaluated with respect to its impact on future cardiometabolic health. Obesity and associated cardiometabolic diseases require a more depth insight into the quality of lipoprotein particles. Further application of omics-based techniques would enable a more comprehensive evaluation of dyslipidemia in order to reduce an excessive cardiovascular risk attributable to increased body weight. However, more studies on obesity-related female reproductive disorders are needed for this approach to be adopted in daily clinical practice.
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Enfermedades Cardiovasculares , Dislipidemias , Femenino , Humanos , Proteómica , Lipoproteínas/metabolismo , Obesidad/complicacionesRESUMEN
Oxidative stress is the consequence of an overproduction of reactive oxygen species (ROS) that exceeds the antioxidant defense mechanisms. Increased levels of ROS contribute to the development of cardiovascular disorders through oxidative damage to macromolecules, particularly by oxidation of plasma lipoproteins. One of the most prominent features of atherogenic dyslipidemia is plasma accumulation of small dense LDL (sdLDL) particles, characterized by an increased susceptibility to oxidation. Indeed, a considerable and diverse body of evidence from animal models and epidemiological studies was generated supporting oxidative modification of sdLDL particles as the earliest event in atherogenesis. Lipid peroxidation of LDL particles results in the formation of various bioactive species that contribute to the atherosclerotic process through different pathophysiological mechanisms, including foam cell formation, direct detrimental effects, and receptor-mediated activation of pro-inflammatory signaling pathways. In this paper, we will discuss recent data on the pathophysiological role of oxidative stress and atherogenic dyslipidemia and their interplay in the development of atherosclerosis. In addition, a special focus will be placed on the clinical applicability of novel, promising biomarkers of these processes.