Rosuvastatin and vascular oxidative stress induced by diesel exhaust particles

Abstract

Objective Exposure to diesel exhaust particles (DEP) is strongly linked to the development and exacerbation of cardiovascular diseases. Statins are effective drugs in the prevention and treatment of cardiovascular disorders. The aim of this study was to investigate the potential protective effect of rosuvastatin on DEP-induced endothelial dysfunction.Methods and results Spontaneously hypertensive rats (SHR) were treated for 5 weeks with rosuvastatin and exposed, intratracheally, for the last 4 weeks, to either DEP suspensions or saline vehicle. Rings of thoracic aortas were used to assess superoxide anion production through the lucigenin-enhanced chemiluminescence technique. Real-time quantitative polymerase chain reaction analysis was performed on aortic segments to assess eNOS, iNOS, p22phox, gp91phox, Rac-1 and TNF- αmRNA expression. Human umbilical vein endothelial cells (HUVECs) were also used for the measurement of oxidative stress after DEP and/or rosuvastatin incubation.In thoracic aortic rings isolated from SHR, superoxide anion formation was increased after DEP exposure. This oxidative stress was markedly decreased in the rosuvastatin-treated group. DEP exposure also induced a downregulation of eNOS mRNA expression and a slight increase in gp91phox mRNA expression, which were reversed in the rosuvastatin group. In HUVECs, similar results were observed: DEP generated an accumulation of superoxide anion, which was significantly attenuated by rosuvastatin.Conclusions Our results suggest that rosuvastatin interacts with the eNOS and NADPH oxidase pathways in hypertensive rats and therefore might counteract the oxidative stress induced by DEP. This effect was also observed in vitroin human endothelial cells (HUVECs).