Endothelial Cells Inhibit the Angiotensin II Induced Phenotypic Modulation of Rat Vascular Adventitial Fibroblasts

The phenotypic modulation of vascular adventitial fibroblasts plays an important role in vascular remodeling. Evidence have shown that endothelial cells and adventitial fibroblasts interact under certain conditions. In this study, we investigated the influence of endothelial cells on the phenotypic modulation of adventitial fibroblasts. Endothelial cells and adventitial fibroblasts from rat thoracic aorta were cultivated in a co-culture system and adventitial fibroblasts were induced with angiotensin II (Ang II). Collagen I and alpha smooth muscle actin (alpha-SMA) expression and migration of adventitial fibroblasts were analyzed. Ang II upregulated the expression of collagen I and alpha-SMA and the migration of adventitial fibroblasts. Adventitial fibroblasts-endothelial cells co-culturing attenuated the effects of Ang II. Homocysteinetreated endothelial cells, which are functionally impaired, were less inhibitory of the phenotypic modulation of adventitial fibroblasts. Supplementation of endothelial cells with L-arginine (L-Arg) or 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) enhanced the trends, while with L-NG-nitroarginine methyl ester (L-NAME) or 1H-[1,2,4] Oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) the opposite effect was observed. Under the influence of Ang II, adventitial fibroblasts were prone to undergo phenotypic modulation, which was closely related to vascular remodeling. Our study showed that endothelial cells influenced fibroblast phenotypic transformation and such effect would be mediated through the nitric oxide (NO)/cGMP signaling pathway. (C) 2017 Wiley Periodicals, Inc.