RESUMO
BACKGROUND: Children living at high altitude in San Antonio de los Cobres (SAC), Argentina, were shown to have lower high-density lipoprotein cholesterol (HDL-C) levels than Buenos Aires (BA) children. HDL antioxidant capacity is mainly attributed to paraoxonase1 (PON1). OBJECTIVE: To compare PON1 activity in indigenous SAC vs. BA children. METHODS: A cross-sectional study compared 158 SAC vs. 97 BA children (6-16 years). Anthropometric data and lipoprotein profile were measured. PON1 was evaluated employing paraoxon (PON) and phenylacetate (ARE) activity. RESULTS: The prevalence of overweight/obesity was lower in SAC than in BA children (18.3 vs. 30.9%). Triglycerides (1.34 vs. 0.90â mmol/l), apo B (0.84 vs.0.72â g/l), apo A-I (1.33 vs. 1.27â g/l), and ARE activity (100 vs. 90â µmol/ml/min) were higher, while HDL-C (1.16 vs. 1.32â mmol/l) and PON activity (170 vs. 203â nmol/ml/min) were lower in SAC than in BA. Separate multiple linear regression analyses showed that SAC children had significantly higher triglyceride (Beta -0.38), apo B (Beta -0.34), and ARE (Beta -0.36) plus lower HDL-C (Beta 0.33) and PON (Beta 0.25) compared with BA; adjusted for age, gender, and BMI. CONCLUSION: SAC showed an unfavorable lipoprotein profile, lower PON and higher ARE activities compared with BA children, suggesting the presence of altered HDL metabolism and antioxidant capacity.
Assuntos
Arildialquilfosfatase/sangue , Obesidade Infantil/enzimologia , Adolescente , Altitude , Apolipoproteína A-I/sangue , Argentina/epidemiologia , Argentina/etnologia , Arildialquilfosfatase/genética , Arildialquilfosfatase/metabolismo , Criança , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Lipídeos/sangue , Masculino , Obesidade Infantil/epidemiologia , Fenilacetatos/metabolismo , Fatores de Risco , Triglicerídeos/sangueRESUMO
Introducción Las HDL ejercen potentes actividades antiaterogénicas, que están exacerbadas en las HDL pequeñas y densas, y pueden estar comprometidas en condiciones de inflamación crónica como la artritis reumatoidea (AR). Sin embargo, las relaciones de función-estructura de HDL permanecen indeterminadas. OBJETIVOS Evaluar la capacidad antiaterogénica de las HDL y sus determinantes moleculares en pacientes con AR en comparación con sujetos controles. MÉTODOS Se realizó un estudio transversal. Se evaluó a 44 pacientes con AR y 33 controles sanos. Se evaluó el perfil metabólico, la actividad de proteínas y enzimas asociadas a lipoproteínas, marcadores de inflamación y composición química y funcionalidad de las HDL. Las relaciones entre la estructura y la función de las HDL sólo fueron evaluadas en un subgrupo de pacientes con AR activa normolipidémicos (n=12) y en controles normolipidémicos de edad semejante (n=10). Se aislaron HDL3b y 3C pequeñas y densas, se evaluaron sus características fisicoquímicas, la lipidómica y la función antioxidante. RESULTADOS En pacientes con AR activa, los niveles más bajos de C-HDL fueron significativos. No se observó alteración en niveles de glucosa ni resistencia a la insulina. El subgrupo con AR activa y normolipemia presentó niveles significativamente elevados de PCRus (p<0,001) respecto a los controles. La actividad antioxidante y la composición química de las HDL pequeñas y densas no difirió entre los pacientes y controles; el fosfoesfingolipidoma de HDL se alteró significativamente en AR. En pacientes con AR con altos niveles de inflamación, la actividad antioxidante de las HDL pequeñas y densas se encontraba reducida (p<0,01), y la actividad antioxidante de HDL se correlacionó inversamente con PCRus (p<0,01). DISCUSIÓN En la AR el lipidoma de las HDL pequeñas y densas se encuentra alterado; posiblemente el estado inflamatorio elevado sea responsable de la disfuncionalidad de las HDL.
Assuntos
Artrite Reumatoide , Inflamação , HDL-ColesterolRESUMO
CONTEXT: Acromegaly is characterized by GH excess and insulin resistance. It is not known which of these disorders is responsible for the increased atherogenic risk in these patients. OBJECTIVE: To analyse the associations of GH and homoeostasis model assessment (HOMA) with biomarkers of cardiovascular disease and to compare the above-mentioned variables between patients with active acromegaly and controls. DESIGN AND SETTING: This open cross-sectional study was conducted at a University Hospital. PATIENTS: Twenty-two outpatients were compared with sex- and age-matched control subjects. MAIN OUTCOMES: Included clinical features, hormonal status, markers of insulin resistance, lipoprotein profile and biomarkers of cardiovascular disease. RESULTS: Patients presented higher triglyceride (median [IQR]) (1·2[1·1-1·6] vs 0·9[0·6-1·1] mm, P < 0·05), low-density lipoprotein-cholesterol (LDL-C) (mean ± SD) (3·5 ± 0·9 vs 3·0 ± 0·7mm, P < 0·05), apoB (0·98 ± 0·23 vs 0·77 ± 0·22 g/l, P < 0·05), free fatty acid (0·69 ± 0·2 vs 0·54 ± 0·2 mM, P < 0·05), oxidized-LDL (120 ± 22 vs 85 ± 19 U/l, P < 0·05) and endothelin-1 (0·90 ± 0·23 vs 0·72 ± 0·17 ng/l, P < 0·05) levels, increased cholesteryl ester transfer protein (CETP) activity (179 ± 27 vs 138 ± 30%/ml/h, P < 0·01) and lower C reactive protein (CRP) (0·25[0·1-0·9] vs 0·85[0·4-1·4] mg/l; P < 0·05) levels than control subjects. Vascular cell adhesion molecule (VCAM-1) concentration was not different. By multiple linear regression analyses, HOMA explained the variability of triglycerides (25%), high-density lipoprotein-cholesterol (HDL-C) (30%) and CETP activity (28%), while GH independently predicted LDL-C (18%), oxidized-LDL (40%) and endothelin-1 levels (19%). CONCLUSIONS: In patients with active acromegaly, GH excess contributes to the development of insulin resistance, and the interaction between both disturbances would be responsible for the appearance of atherogenic pro-oxidative and pro-inflammatory factors. Insulin resistance would be preferably associated with an atherogenic lipoprotein profile and to high CETP activity, while high GH levels would independently predict the increase in LDL-C, ox-LDL and endothelin-1.
Assuntos
Acromegalia/sangue , Doenças Cardiovasculares/metabolismo , Hormônio do Crescimento/sangue , Resistência à Insulina/fisiologia , Acromegalia/metabolismo , Adulto , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIMS: Metabolic syndrome (MS) and type 2 diabetes are highly associated with an abnormal lipoprotein profile, which may be generated and accentuated by high cholesteryl ester transfer protein (CETP) activity. Given the difficulty in measuring CETP activity, the aim was to identify simple biochemical predictors of high CETP activity. DESIGN AND METHODS: Eighty five subjects at risk for type 2 diabetes were classified according to the presence of MS. Lipoprotein profile, HOMA-IR and endogenous CETP activity were evaluated. RESULTS: As expected, MS patients presented higher concentration of glucose, insulin, triglycerides and non-HDL-C and lower HDL-C levels. Moreover, MS patients exhibited increased HOMA-IR and CETP activity. Employing a ROC curve for MS, high CETP activity was defined as >250%ml⻹ h⻹. The predictive variables of high CETP were non-HDL-C≥160mg/dl (OR=11.1;95%IC=3.3-38.2;p<0.001) and HOMA-IR>2.1 (OR=4.4;95%IC=1.3-14.8;p<0.05). CONCLUSIONS: High non-HDL-C and insulin resistance were predictors for increased CETP activity which measurement is not accessible for clinical laboratories.
Assuntos
Proteínas de Transferência de Ésteres de Colesterol/metabolismo , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/patologia , Resistência à Insulina , Biomarcadores/sangue , Biomarcadores/metabolismo , Glicemia , Índice de Massa Corporal , Estudos de Casos e Controles , Proteínas de Transferência de Ésteres de Colesterol/sangue , HDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Modelos Lineares , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Fatores de Risco , Circunferência da CinturaRESUMO
OBJECTIVES: In acromegalic patients, cardiovascular and metabolic comorbidities contribute to enhance mortality. Available data on the lipoprotein profile of these patients are controversial. Our aim was to characterize the lipoprotein profile and emergent biomarkers of cardiovascular disease in active acromegalic patients in comparison with sex- and age-matched healthy controls. PATIENTS: Eighteen patients with active acromegaly and 18 controls were studied. MEASUREMENTS: Glucose levels, hormonal status, lipoprotein profile and C reactive protein (CRP) were evaluated by standardized methods. Cholesteryl ester transfer protein (CETP) and lipoprotein-associated phospholipase A(2 )(Lp-PLA(2)) were measured by radiometric techniques, endothelin-1 and vascular cell adhesion molecule (VCAM)-1 by enzyme-linked immunosorbent assay, and leucocytes CD18, CD49d and CD54 by flow cytometry. RESULTS: After adjusting for body mass index (BMI), acromegalic patients presented a more atherogenic lipoprotein profile, consisting of higher levels of triglycerides and apolipoprotein B and alterations in the ratios which estimate insulin resistance and atherogenic risk. CETP activity was significantly increased in acromegalic patients as compared to controls (168 +/- 17 vs. 141 +/- 30% per ml h, respectively; P < 0.05). Endothelin-1 levels evidenced an increase in the patients' group (0.9 +/- 0.2 vs. 0.7 +/- 0.2 ng/l, respectively; P < 0.01) and showed positive and significant correlations with GH, IGF-1 and IGFBP-3 (r = 0.45, 0.42 and 0.44, respectively; P < 0.01 for all of them; with BMI as a fixed variable). Lymphocytes from acromegalic patients showed increased CD49d content (282 +/- 59 vs. 246 +/- 48 arbitrary units, respectively; P < 0.05). CONCLUSIONS: Taken together, the alterations described seem to contribute to constituting a state of higher propensity for the development of atherosclerotic cardiovascular disease, which adds to the presence of specific cardiomyopathy.
Assuntos
Acromegalia/complicações , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Adulto , Idoso , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Antígenos CD18/sangue , Proteínas de Transferência de Ésteres de Colesterol , Endotelina-1/sangue , Feminino , Humanos , Integrina alfa4/sangue , Molécula 1 de Adesão Intercelular/sangue , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
BACKGROUND AND AIMS: Adiponectin is an adipokine highly and specifically expressed by adipose cells with antiatherogenic and antiinflammatory activities. The aim of the present study was to evaluate plasma adiponectin concentration in patients with primary hypertriglyceridemia and its relationship with metabolic parameters. METHODS AND RESULTS: Male patients with primary hypertriglyceridemia and without the metabolic syndrome (n=22) were compared with normotriglyceridemic individuals (n=25). Plasma adiponectin concentration was measured by standardised enzyme-linked immunosorbent assay. Body mass index, waist circumference, glucose, insulin and non-esterified fatty acid levels, lipoprotein profile, and CETP activity were evaluated. Adiponectin levels were significantly decreased in hypertriglyceridemic patients in comparison with normotriglyceridemic subjects (4292+/-1717 vs. 6939+/-3249 ng/ml, p<0.005, respectively). Adiponectin was negatively associated with glucose (r=-0.44, p<0.01), insulin (r=-0.37, p<0.01), HOMA (r=-0.40, p<0.01), triglycerides (r=-0.36, p<0.01), VLDL-C (r=-0.34, p<0.05), and CETP (r=-0.47, p<0.001). Positive and significant correlations were observed with QUICKI (r=0.49, p<0.001) and HDL-C (r=0.33, p<0.05). In the multiple linear regression analysis, considering waist circumference, QUICKI, Log-triglycerides, HDL-C, and CETP as independent variables, Log-adiponectin showed a positive correlation with QUICKI, with an r(2)=0.229 and p<0.001. Therefore, the independent variable QUICKI explained the 23% of the variance in Log-adiponectin concentration. CONCLUSIONS: We found low adiponectin levels in a population of primary hypertriglyceridemic men without the metabolic syndrome and an independent relationship between adiponectin concentration and insulin resistance. A reduction in insulin sensitivity and its impact on adiponectin concentration could be linked to high non-esterified fatty acid levels, increased triglyceride synthesis in the liver and impaired catabolism of triglyceride-rich lipoproteins.
Assuntos
Hipertrigliceridemia/sangue , Síndrome Metabólica/sangue , Triglicerídeos/sangue , Adiponectina/sangue , Glicemia/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Proteínas de Transferência de Ésteres de Colesterol/sangue , Regulação para Baixo , Ácidos Graxos não Esterificados/sangue , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/fisiopatologia , Insulina/sangue , Resistência à Insulina , Lipoproteínas/sangue , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/fisiopatologia , Fatores Sexuais , Circunferência da CinturaRESUMO
This paper describes the beneficial effects of rosuvastatin in patients with arterial hypertension in ventricular remodeling. As a conclusion, our data supports new evidence to encourage the use of statins for the treatment of cronic arterial hypertension and venticular remodeling
Assuntos
Coelhos , Coleta de Amostras Sanguíneas , Colesterol/análise , Ecocardiografia Doppler , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares , Hipertensão/patologia , Hipertensão/terapia , Inibidores de Hidroximetilglutaril-CoA RedutasesRESUMO
BACKGROUND: In postmenopausal women (PMW), an adverse lipoprotein pattern and high risk of coronary artery disease has been described. Studies of the mechanisms promoting the higher atherogenic risk observed in healthy PMW are relevant. We evaluated the interactions among several circulating factors involved in the endothelial injury and inflammation in relation to LDL characteristics, beyond LDL cholesterol. METHODS: Lipoprotein profile, including apolipoproteins A-I and B, small dense LDL, hepatic lipase, cholesterol transfer protein (CETP), LDL composition and oxidability were assessed in PMW (n=30) in comparison to premenopausal (PreMW, n=28). The following emerging factors were measured: homocysteine, phospholipase A2, ferritin, hs-CRP and fibronectin from extracellular vascular matrix. Insulin-resistance was evaluated by waist circumference, HOMA and TG/HDL cholesterol ratios. RESULTS: The risk index apo B/apo A-I was significantly increased in PMW (p<0.0001), PMW showed higher proportion of small dense LDL which correlated with the increase in hepatic lipase activity (p<0.005) and with insulin-resistance markers (p<0.05), but not with CETP. Phospholipase A2 (p<0.05), homocysteine (p<0.005), hs-CRP (p<0.005), fibronectin (p<0.05) and ferritin (p<0.0001) were increased in PMW. LDL oxidability positively correlated with waist (p<0.02), homocysteine (p<0.05), fibronectin (p<0.05), hs-CRP (p<0.04), phospholipase A2 (p<0.05), and small dense LDL (p<0.01). After adjusting by menopausal condition, age and waist, LDL oxidability remained associated with waist (beta: 0.35, p=0.047), homocysteine (beta: 0,36 p<0,038), fibronectin (beta: 0,41 p=0.05), and small dense LDL (beta: 0.36, p=0.027). CONCLUSIONS: Evaluation of classic and non-traditional circulating risk factors in hypoestrogenism reflected endothelial and subendothelial inflammation and subclinical atherogenic processes.
Assuntos
Endotélio Vascular/patologia , Fibronectinas/sangue , Lipoproteínas LDL/sangue , Pós-Menopausa/sangue , Adulto , Antropometria , Biomarcadores , Feminino , Humanos , Resistência à Insulina , Lipase/sangue , Lipase Lipoproteica/sangue , Fígado/enzimologia , Pessoa de Meia-Idade , Oxirredução , Valores de Referência , Relação Cintura-QuadrilRESUMO
BACKGROUND: Lipoprotein lipase (LPL) deficiency is a rare autosomal recessively inherited disease characterized by elevated triglyceride, low total cholesterol and quantitative and qualitative alterations of high-density lipoprotein (HDL). The aim of the present study was to explore HDL metabolic activities in a patient with LPL deficiency and in his family (n = 11). MATERIALS AND METHODS: Subjects were divided into four groups: proband (Ser447Stop/Arg170Leu carrier), Ser447Stop carriers, Arg170Leu carriers and silent mutation/wild-type carriers (controls). Cholesterol efflux from Fu5AH cells, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), paraoxonase 1 (PON1) and platelet-activating factor acetylhydrolase (PAF-AH) activities were evaluated. RESULTS: Comparison between the proband and the control group revealed that the boy had significantly reduced cholesterol efflux (P < 0.001), conserved LCAT activity (P > 0.05) and increased CETP activity (P < 0.001). As regards antioxidant enzymes, while PON1 activity was higher in the proband than in the controls (P < 0.0001), PAF-AH activity was reduced (P < 0.05). The other groups did not show relevant differences in comparison with controls. CONCLUSIONS: The presence of one mutation was not enough to introduce important modifications in HDL functions. Markedly reduced HDL levels can keep certain normal enzymatic activities, which probably tend to counteract the deleterious effects of LPL deficiency.
Assuntos
HDL-Colesterol/metabolismo , Lipase Lipoproteica/deficiência , Apolipoproteína A-I/metabolismo , Apolipoproteína A-II/metabolismo , Arildialquilfosfatase/metabolismo , Proteínas de Transporte/metabolismo , Pré-Escolar , Proteínas de Transferência de Ésteres de Colesterol , Feminino , Glicoproteínas/metabolismo , Heterozigoto , Humanos , Lipase Lipoproteica/genética , Masculino , LinhagemRESUMO
UNLABELLED: The case is reported of a 4-y-old boy with chylomicronaemia syndrome, under treatment with a low-fat diet and medium-chain triglycerides. The clinical and biochemical characteristics of the patient and 11 members of his family were studied. Lipoprotein profile, lipoprotein lipase (LPL) mass and activity were evaluated. Nucleotide substitutions in LPL promoter and exons were screened. The proband presented with severe hypertriglyceridaemia (triglycerides = 13.25 mmol l(-1)) and non-detectable LPL activity and mass. The boy was a compound heterozygote for four molecular defects in the LPL gene, two of which have not been reported before (CGT764 CTT/Arg170 --> Leu; GGA1482 --> GGT/Gly409 --> Gly). Among the family members, the proband was the only one who carried two genetic variants that modify LPL amino acid composition. CONCLUSION: The association of different alterations in the LPL gene could be a key factor in causing the severe phenotype observed. Moreover, treatment with a low-fat diet and medium-chain triglycerides failed to normalize the patient's hypertriglyceridaemia.