A12570 Angiotensin II Type 1 Receptor mediates the Expression of Collagen Type 1 in Homocysteine stimulated Rat Adventitial Fibroblasts by ERK1/2-STAT3 pathway

Abstract

Objectives: We aimed to explore Homocysteine (Hcy) on the expression of collagen type 1 and angiotensin II type 1 receptor (AT1 R) in rat aortic adventitial fibroblasts (AFs), and to investigate the mechanism and signaling pathway of Hcy aggravated vascular remodeling Methods: The Paste tissue pieces method was used to cultivate original generation fibroblasts of adventitia isolated from thoracic aorta of male Sprague-Dawley rats. AFs were divided into four groups: Control group: cultured cells without Hcy; Hcy group: AFs stimulated by Hcy at different concentration (50, 100, 200 μmol/L) and different time (12, 24, 48 hours); Hcy+U0126 group: AFs were pretreated with U0126 (ERK1/2 blocker, 10 μmol/L) for 30 min, then stimulated by Hcy (100 μmol/L) for 24 h; DMSO group: AFs stimulated by DMSO (10 μmol/L) for 24 h. The expression of collagen type 1, AT1 R, p-ERK1/2, p-STAT3 and t-ERK1/2 were measured by western blot Results: With the increase of concentration and treated time of Hcy, the expression of collagen type 1 and AT1 R increased, and the maximal effect appears at concentration of 100 μmol/L Hcy and at 48 h. This dose- and time-response fashion was also observed in the expression of p-STAT3 and p-ERK1/2. U0126 (10 μmol/L) could significantly block the pathway of ERK1/2- STAT3 and then inhibit the expression of collagen type 1 and AT1 R, compared with 100 μmol/L Hcy group Conclusion: Hcy could increase the expression of collagen type 1 and AT1 R in AFs in rats, which is partly through the activation of ERK1/2- STAT3 signal pathway, contributing to the development of vascular remodeling. This effect could significantly inhibit by ERK1/2 blocker-U0126