Angiotensin II Stimulation of NADPH oxidase Activity and Secretion of Cyclophilin-A in Adventitial Fibroblasts; Potential Role in the Paracrine Mediation of Vascular Smooth Muscle Cell Hypertrophy

Abstract

Superoxide (02) derived from NADPH oxidase is thought to contribute to the cause of hypertension. O2 is found at elevated levels in many disease states such as atherosclerosis, diabetes, and restenosis. It has been reported that angiotensin II (AngII) stimulates NADPH oxidase-derived reactive oxygen species in the adventitia and intima concomitant with medial hypertrophy (Rey et al., 2002). We hypothesized that increasing the activity of NADPH oxidase in adventitial fibroblasts with angiotensin II causes the release of hormones that increase hypertrophy of the media, and that these factors increase hypertrophy by activating the ERKI/2 pathway. To better understand how the adventitia might affect medial hypertrophy, fibroblasts, the major cell type in the adventitia, were studied. Using an NADPH oxidase activity assay, a proliferation assay, and Western blotting, we determined that the proliferation of fibroblasts and secretion of cyclophilin-a in response to AngII were NADPH oxidase dependent.