Efecto de la atorvastatina sobre la expresión vascular de los PPAR en conejos dislipémicos

Laburpena

Introduction The family of peroxisome proliferator-activated receptors (PPARs) displays anti-inflammatory and anti-oxidant effects, as well as some effects that act on lipid and glucose metabolism. Statins show certain effects similar to those of PPARs, and consequently it has been suggested that these drugs could exert their antiatherogenic effects by means of PPAR modulation. Aim To evaluate the effect of dyslipidemia and atorvastatin treatment on vascular expression of PPARα, β/δ and γ, endothelial function, and atherosclerotic lesions. Material and method Male New Zealand rabbits were fed a 1% cholesterol-enriched diet with or without atorvastatin (1 mg/kg/day) for 10 weeks. A group of animals fed a standard diet was used as a control. At the end of the treatment, responses to acetylcholine (10−9-10−5 mol/l) and sodium nitroprusside were evaluated (10−10-10−6 mol/l). Morphometric analysis of the aorta was performed, as well as real time RT-PCT to measure vascular expression of PPARα, β/δ and γ. Results Animals fed a cholesterol-enriched diet had higher levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides than controls. Dyslipidemia was associated with intimal thickening and reductions in acetylcholine relaxation and PPARα and γ vascular expression. Atorvastatin treatment normalized triglyceride levels and reduced those of total cholesterol and LDL-cholesterol but was not able to normalize them. This drug also prevented reductions in acetylcholine relaxation and PPAR expression and reduced atherosclerotic lesion size. Neither dyslipidemia nor atorvastatin treatment modified PPARβ/δ expression. Conclusions These data suggest that dyslipidemia exerts varying effects on aortic PPAR expression, reducing PPARα and γ while not modifying PPARβ/δ. The increased PPARα and γ expression observed with atorvastatin administration could mediate the anti-atherogenic effects exerted by this statin.