Open AccessImatinib attenuates cardiac fibrosis by inhibiting platelet-derived growth factor receptors activation in isoproterenol induced model
Author(s) -
Le-Xun Wang,
Xiao Yang,
Yue Yuan,
Tingting Fan,
Jian Hou,
Guangxian Chen,
Mengya Liang,
Zhongkai Wu
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0178619
Subject(s) - fibrosis , cardiac fibrosis , western blot , medicine , myocardial fibrosis , platelet derived growth factor receptor , transforming growth factor , receptor , growth factor , muscle hypertrophy , endocrinology , pharmacology , cancer research , chemistry , gene , biochemistry
Cardiac fibrosis is a significant global health problem with limited treatment choices. Although previous studies have shown that imatinib (IMA) inhibited cardiac fibrosis, the anti-fibrotic mechanisms have not been clearly uncovered. The aim of this study is to evaluate whether IMA attenuates cardiac fibrosis by inhibiting platelet-derived growth factor receptors (PDGFR) on isoproterenol (ISO)-induced mice. Adult male C57BL/6 mice were treated with vehicle or ISO ± IMA for one week. After echocardiography examination, the hearts of mice were used for histopathologic, RT-qPCR, and western blot analyses. We found that the ventricular wall thickness, cardiac hypertrophy, and apoptosis were enhanced following ISO treatment. IMA decreased the left ventricular wall thickness, prevented hypertrophy, and inhibited apoptosis induced by ISO. In addition, IMA attenuated the accumulation of collagens and α-smooth muscle actin (α-SMA) (the markers of fibrosis) caused by ISO treatment. Moreover, the expression of fibrosis related genes, and the phosphorylation of PDGFRs in ISO-treated mice hearts were inhibited by IMA as well. However, IMA did not change the expression of the matrix metalloproteinase-9 (MMP-9) in ISO-treated hearts. Furthermore, IMA reduced the expressions of collagens as well as α-SMA caused by activation of PDGFRα in cardiac fibroblasts. Taken together, our data demonstrate that IMA attenuated the cardiac fibrosis by blocking the phosphorylation of PDGFRs in the ISO-induced mice model. This study indicates that IMA could be a potentially therapeutic option for cardiac fibrosis in clinical application.