title: Effects of intermedin1-53 on myocardial fibrosis.
abstract: Intermedin (IMD) is a member of the calcitonin/calcitonin gene-related peptide (CGRP) family and has similar or more potent cardiovascular actions than adrenomedullin (ADM) and any other CGRP. The aim of the present work is to study the effects of IMD1-53 on cardiac fibroblast fibrosis in vivo and in vitro. Myocardial infarction model was prepared by ligating rats' left anterior descending coronary artery. Mesenchymal collagen contents in the left ventricle were accessed by Sirius-red stain. Heart functions were explored by hemodynamic changes. Expression of I and III type collagens, IMD1-53, receptor activity-modifying proteins (RAMP)1/2/3, and calcitonin receptor-like receptor (CRLR) in left ventricle were detected by western blot analysis. Cardiac fibroblasts (CFbs) fibrosis was induced by treating the cells with aldosterone (ALD). CFbs proliferation and the hydroxyproline contents in supernatants were determined by 3-[4,5-dimehyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide assay and enzyme-linked immunosorbent assay. Heart function was decreased in myocardial infarction model rats. Expression of type I and type III collagens in infarcted zone in myocardial rats was higher than those in the sham-operated group. IMD1-53, RAMP, and CRLR in left ventricle were also up-regulated. In vitro experiment showed that ALD was a powerful stimulator of CFbs activation. IMD1-53 decreased ALD-induced CFbs proliferation in a dose-dependent manner. Moreover, CGRP8-37 and ADM22-52 remarkably blocked the effect of IMD1-53 on ALD-induced myocardial cell fibrosis. IMD could be involved in the onset of cardiac fibrosis. Like ADM, IMD1-53 exerts an antifibrotic effect on CFbs, which might be mediated by CRLR/RAMP complex and ADM receptor.
authors.affiliation: Department of Pathophysiology, Basic Medical School,  Ningxia Medical University, Yinchuan 750004,  China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhang
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Jia
authors.forename: Lan
authors.initials: L
authors.lastname: Ni
authors.forename: Guizhong
authors.initials: G
authors.lastname: Li
authors.forename: Lihua
authors.initials: L
authors.lastname: Xue
authors.forename: Yideng
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004719:Endomyocardial Fibrosis / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C499411:Adm2 protein, rat; D009479:Neuropeptides; D053607:Adrenomedullin