Effects of adrenomedullin on angiotensin II-induced collagen synthesis in vascular adventitial fibroblasts
Liu, H-chao.; Ma, Y-xin.; He, J.; Ke, J.
Zhonghua Xin Xue Guan Bing Za Zhi 35(9): 848-853
2007
ISSN/ISBN: 0253-3758 PMID: 18070482 Document Number: 611877
Objective To explore the effects of adrenomedullin (ADM) on Angiotensin II (Ang II)-induced collagen synthesis in cultured rat vascular adventitial fibroblasts. Methods Rat vascular adventitial fibroblasts were cultured in vitro. ADM produced and secreted from adventitia in the presence of Ang II was detected by radioimmunoassay, type I, III collagen contents in adventitia fibroblasts were measured by ELISA and the expressions of TGF beta 1 and MMP-2 were determined by RT-PCR and Western blotting. Results Ang H significantly induced ADM secretion in adventitial fibroblasts in a dose-dependent manner. These effects could be reduced by 45%, 3% and 46%, through pre-treatment with Losartan, PD123319 or both, respectively for 30 min in culture medium. The Ang II-induced type I, III collagen secretion in adventitial fibroblasts was significantly reduced by AMD in a dose-dependent manner, (P < 0.01) while ADM agonist ADM(22-52) significantly potentiated the effect of Ang II; ADM also reduced Ang II induced expression of TGF beta 1 at mRNA and protein levels in a dose-dependent manner. Ang II reduced the expression of MMP-2 at mRNA and protein levels in adventitial fibroblasts and these effects could be reversed by AMD(10(-8) mol/L). Conclusion Ang II stimulated ADM secretion in adventitia fibroblasts, ADM in turn can inhibit Ang II -induced type I, III collagen synthesis in adventitial fibroblasts probably by downregulating the TGF beta 1 expression and upregulating MMP-2 expression. ADM therefore served as an antifibrotic factor in vascular remodeling process.