Alteration of p66shc is associated with endothelial dysfunction in the abdominal aortic coarctation of rats

Abstract 

To examine the role of p66shc in endothelial dysfunction, we investigated the endothelium-dependent relaxation, protein expression and superoxide production in abdominal aortic coarctation rats. Endothelium-dependent relaxation to acetylcholine was impaired only in the aortic segments above the aortic coarctation (35.0±7.1% vs. 86.6±6.0% for sham control at 1μM Ach). The aortic segments exposed to increased blood pressure showed a decreased phosphorylation of endothelial nitric oxide synthase, an increased phosphorylation of p66shc, and an increased superoxide production. Angiotensin II elicited a significantly increased phosphorylation of p66shc in the endothelial cells. Taken together, these findings suggest that the increased phosphorylation of p66shc is one of the important mediators in the impaired endothelium-dependent relaxation of aortic coarctation rats.

Abbreviations: eNOS, endothelial nitric oxide synthase, Ach, acetylcholine, NO, nitric oxide, ROS, reactive oxygen species, Shc, src homology and collagen, Mn SOD, manganese superoxide dismutase, Cu/Zn SOD, copper/zinc superoxide dismutase, MS-1, mouse endothelial cells

Keywords: p66shc, Aortic coarctation, Endothelium-dependent relaxation, Endothelial nitric oxide synthase, Superoxide