RESUMO
Although the Mediterranean diet (MD) and the low-fat Therapeutic Lifestyle Changes Diet (TLCD) promote equivalent increases in event-free survival in secondary coronary prevention, possible mechanisms of such complete dietary patterns in these patients, usually medicated, are unclear. The aim of this study was to investigate the effects of the MD versus the TLCD in markers of endothelial function, oxidative stress, and inflammation after acute coronary syndromes. Comparison was made between 3 months of the MD (n = 21; rich in whole grains, vegetables, fruits, nuts, and olive oil, plus red wine) and the TLCD (n = 19; plus phytosterols 2 g/day) in a highly homogenous population of stable patients who experienced coronary events in the previous 2 years (aged 45 to 65 years, all men) allocated to each diet under a strategy designed to optimize adherence, documented as >90%. Baseline demographics, body mass index and clinical data, and use of statins and other drugs were similar between groups. The MD and TLCD promoted similar decreases in body mass index and blood pressure (p ≤0.001) and particularly in plasma asymmetric dimethylarginine levels (p = 0.02) and l-arginine/asymmetric dimethylarginine ratios (p = 0.01). The 2 diets did not further enhance flow-mediated brachial artery dilation compared to baseline (4.4 ± 4.0%). Compared to the TLCD, the MD promoted decreases in blood leukocyte count (p = 0.025) and increases in high-density lipoprotein levels (p = 0.053) and baseline brachial artery diameter. Compared to the MD, the TLCD decreased low-density lipoprotein and oxidized low-density lipoprotein plasma levels, although the ratio of oxidized to total low-density lipoprotein remained unaltered. Glucose, high-sensitivity C-reactive protein, triglycerides, myeloperoxidase, intercellular adhesion molecular, vascular cell adhesion molecule, and glutathione serum and plasma levels remained unchanged with either diet. In conclusion, medicated secondary prevention patients show evident although small responses to the MD and the TLCD, with improved markers of redox homeostasis and metabolic effects potentially related to atheroprotection.
Assuntos
Aterosclerose/prevenção & controle , Biomarcadores/sangue , Dieta com Restrição de Gorduras , Dieta Mediterrânea , Inflamação/sangue , Cooperação do Paciente , Prevenção Secundária/métodos , Idoso , Aterosclerose/sangue , Proteína C-Reativa/metabolismo , Seguimentos , Humanos , Estilo de Vida , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Triglicerídeos/sangueRESUMO
The signalling pathway CD40/CD40L (CD40 ligand) plays an important role in atherosclerotic plaque formation and rupture. AngII (angiotensin II), which induces oxidative stress and inflammation, is also implicated in the progression of atherosclerosis. In the present study, we tested the hypothesis that AngII increases CD40/CD40L activity in vascular cells and that ROS (reactive oxygen species) are part of the signalling cascade that controls CD40/CD40L expression. Human CASMCs (coronary artery smooth muscle cells) in culture exposed to IL (interleukin)-1beta or TNF-alpha (tumour necrosis factor-alpha) had increased superoxide generation and enhanced CD40 expression, detected by EPR (electron paramagnetic resonance) and immunoblotting respectively. Both phenomena were abolished by previous incubation with membrane-permeant antioxidants or cell transfection with p22(phox)antisense. AngII (50-200 nmol/l) induced an early and sustained increase in CD40 mRNA and protein expression in CASMCs, which was blocked by treatment with antioxidants. Increased CD40 expression led to enhanced activity of the pathway, as AngII-treated cells stimulated with recombinant CD40L released higher amounts of IL-8 and had increased COX-2 (cyclo-oxygenase-2) expression. We conclude that AngII stimulation of vascular cells leads to a ROS-dependent increase in CD40/CD40L signalling pathway activity. This phenomenon may be an important mechanism modulating the arterial injury observed in atherosclerosis-related vasculopathy.