RESUMO
Sirtuin-1 (Sirt-1) and an endogenous secretory receptor for an advanced glycation end product (esRAGE) are associated with vascular protection. The purpose of this study was to examine the effects of resveratrol (RSV) and caloric restriction (CR) on gene expression of Sirt-1 and esRAGE on serum levels of Sirt1 and esRAGE in healthy and slightly overweight subjects. The study included 48 healthy subjects randomized to 30 days of RSV (500 mg/day) or CR (1000 cal/day). Waist circumference (p = 0.011), TC (p = 0.007), HDL (p = 0.031), non-HDL (p = 0.025), ApoA1 (p = 0.011), and ApoB (p = 0.037) decreased in the CR group. However, TC (p = 0.030), non-HDL (p = 0.010), ApoB (p = 0.034), and HOMA-IR (p = 0.038) increased in the RSV group. RSV and CR increased serum levels of Sirt-1, respectively, from 1.06 ± 0.71 ng/mL to 5.75 ± 2.98 ng/mL (p < 0.0001) and from 1.65 ± 1.81 ng/mL to 5.80 ± 2.23 ng/mL (p < 0.0001). esRAGE serum levels were similar in RSV (p = NS) and CR (p = NS) groups. Significant positive correlation was observed between gene expression changes of Sirt-1 and esRAGE in RSV (r = 0.86; p < 0.0001) and in CR (r = 0.71; p < 0.0001) groups, but not for the changes in serum concentrations. CR promoted increases in the gene expression of esRAGE (post/pre). Future long-term studies are needed to evaluate the impact of these outcomes on vascular health.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Sobrepeso , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Sirtuína 1/metabolismo , Estilbenos/farmacologia , Idoso , Restrição Calórica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor para Produtos Finais de Glicação Avançada/genética , Resveratrol , Sirtuína 1/genética , Estilbenos/administração & dosagemRESUMO
BACKGROUND: Sirtuin 1 (Sirt1) plays an important role in vascular biology, and influences aspects of age-dependent atherosclerosis. In animals, the sirtuin system is strongly influenced by resveratrol and caloric restriction, but its expression in humans is controversial. This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population. METHODS AND RESULTS: Forty-eight healthy participants (24 women) aged 55-65years were randomized to either 30days of resveratrol administration (500mg/day) or caloric restriction (1000cal/day). Blood was collected at baseline and day 30. Laboratory data analyzed were triglycerides, total cholesterol, HDL, VLDL, LDL, apolipoprotein A1, apolipoprotein B, lipoprotein (a), non-esterified fatty acids (NEFA), glucose, insulin, oxidative stress, C-reactive protein, and Sirt1. Expression of the Sirt1 gene was analyzed using real-time PCR. Caloric restriction diminished the abdominal circumference and improved the lipid profile, but not resveratrol intervention. Resveratrol and caloric restriction increased serum concentrations of Sirt1, from 1.06±0.71 to 5.75±2.98ng/mL; p<0.0001, and from 1.65±1.81 to 5.80±2.23ng/mL; p<0.0001, respectively. Sirt1 increased in women and men in both interventions. On the other hand expression of Sirt1 mRNA was not different after caloric restriction and resveratrol treatment. CONCLUSIONS: Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1. The long-term impact of these interventions on atherosclerosis should be assessed.
Assuntos
Sobrepeso/dietoterapia , Sirtuína 1/sangue , Sirtuína 1/genética , Estilbenos/administração & dosagem , Biomarcadores/sangue , Restrição Calórica , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Sobrepeso/genética , Sobrepeso/metabolismo , Estudos Prospectivos , Resveratrol , Sirtuína 1/biossínteseRESUMO
OBJECTIVE: To examine the association of atherogenic and thrombogenic markers and lymphotoxin-alfa gene mutations with the risk of premature coronary disease. METHODS: This cross-sectional, case-control, age-adjusted study was conducted in 336 patients with premature coronary disease (<50 years old) and 189 healthy controls. The control subjects had normal clinical, resting, and exercise stress electrocardiographic assessments. The coronary disease group patients had either angiographically documented disease (>50% luminal reduction) or a previous myocardial infarction. The laboratory data evaluated included thrombogenic factors (fibrinogen, protein C, protein S, and antithrombin III), atherogenic factors (glucose and lipid profiles, lipoprotein(a), and apolipoproteins AI and B), and lymphotoxin-alfa mutations. Genetic variability of lymphotoxin-alfa was determined by polymerase chain reaction analysis. RESULTS: Coronary disease patients exhibited lower concentrations of HDL-cholesterol and higher levels of glucose, lipoprotein(a), and protein S. The frequencies of AA, AG, and GG lymphotoxin-alfa mutation genotypes were 55.0%, 37.6%, and 7.4% for controls and 42.7%, 46.0%, and 11.3% for coronary disease patients (p = 0.02), respectively. Smoking, dyslipidemia, family history, and lipoprotein(a) and lymphotoxin-alfa mutations in men were independent variables associated with coronary disease. The area under the curve (C-statistic) increased from 0.779 to 0.802 (p<0.05) with the inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors. CONCLUSIONS: The inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors showed an additive but small increase in the risk prediction of premature coronary disease. .
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aterosclerose/genética , Doença da Artéria Coronariana/genética , Linfotoxina-alfa/genética , Aterosclerose/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Doença da Artéria Coronariana/sangue , Predisposição Genética para Doença , Genótipo , Lipoproteínas/sangue , Lipoproteínas/genética , Mutação/genética , Polimorfismo Genético , Valor Preditivo dos Testes , Fatores de Risco , Curva ROC , Trombose/sangue , Trombose/genéticaRESUMO
OBJECTIVE: To examine the association of atherogenic and thrombogenic markers and lymphotoxin-alfa gene mutations with the risk of premature coronary disease. METHODS: This cross-sectional, case-control, age-adjusted study was conducted in 336 patients with premature coronary disease (<50 years old) and 189 healthy controls. The control subjects had normal clinical, resting, and exercise stress electrocardiographic assessments. The coronary disease group patients had either angiographically documented disease (>50% luminal reduction) or a previous myocardial infarction. The laboratory data evaluated included thrombogenic factors (fibrinogen, protein C, protein S, and antithrombin III), atherogenic factors (glucose and lipid profiles, lipoprotein(a), and apolipoproteins AI and B), and lymphotoxin-alfa mutations. Genetic variability of lymphotoxin-alfa was determined by polymerase chain reaction analysis. RESULTS: Coronary disease patients exhibited lower concentrations of HDL-cholesterol and higher levels of glucose, lipoprotein(a), and protein S. The frequencies of AA, AG, and GG lymphotoxin-alfa mutation genotypes were 55.0%, 37.6%, and 7.4% for controls and 42.7%, 46.0%, and 11.3% for coronary disease patients (pâ=â0.02), respectively. Smoking, dyslipidemia, family history, and lipoprotein(a) and lymphotoxin-alfa mutations in men were independent variables associated with coronary disease. The area under the curve (C-statistic) increased from 0.779 to 0.802 (p<0.05) with the inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors. CONCLUSIONS: The inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors showed an additive but small increase in the risk prediction of premature coronary disease.
Assuntos
Aterosclerose/genética , Doença da Artéria Coronariana/genética , Linfotoxina-alfa/genética , Adulto , Aterosclerose/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Estudos Transversais , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lipoproteínas/sangue , Lipoproteínas/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo Genético , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Trombose/sangue , Trombose/genéticaRESUMO
OBJECTIVES: To evaluate clinical and echocardiographic variables that could be used to predict outcomes in patients with asymptomatic severe aortic valve stenosis. Management of asymptomatic severe aortic stenosis is controversial. Because prophylactic surgery may be protective, independent predictors of events that could justify early surgery have been sought. METHODS: Outpatients (n=133; mean [+/-SD] age, 66.2+/-13.6 years) with isolated severe asymptomatic aortic stenosis but normal left ventricular function and no previous myocardial infarction were followed up prospectively at a tertiary care hospital. INTERVENTIONS: We use a "wait-for-events" strategy. Clinical and echocardiographic variables were analyzed. RESULTS: Nineteen patients developed angina; 40, dyspnea; 5, syncope; and 7, sudden death during a mean follow-up period of 3.30+/-1.87 years. Event-free survival was 90.2+/-2.6% at 1 year, 73.4+/-3.9% at 2 years, 70.7+/-4.3% at 3 years, 57.8+/-4.7% at 4 years, 40.3+/-5.0% at 5 years, and 33.3+/-5.2% at 6 years. The mean follow-up period until sudden death (1.32+/-1.11 years) was shorter than that for dyspnea (2.44+/-1.84 years), syncope (2.87+/-1.26 years) and angina (3.03+/-1.68 years). Cox regression analysis disclosed only reduced but within normal limits ejection fraction as independent predictor of total events. CONCLUSIONS: Management on "wait-for-events" strategy is generally safe. Progressive left ventricular ejection fraction reduction even within normal limits identified patients at high risk for events in whom valve replacement surgery should be considered.