Loss of Myeloid-Derived Growth Factor Leads to Increased Fibrosis in Mice After Myocardial Infarction
Objective To investigate the effect of the loss of myeloid-derived growth factor(Mydgf)on the transformation of cardiac fibroblasts into myofibroblasts after myocardial infarction(MI).Methods Two adult mouse groups,including a wild-type(WT)group and another group with Mydgf knockout(Mydgf-KO),were examined in the study.The mice in these two groups were tested for their cardiac function by measuring left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(n=10).Quantitative real-time PCR(qRT-PCR)(n=3)was performed to determine the mRNA expression levels of myofibroblast markers,including α-smooth muscle actin(α-SMA),periostin(postn),type Ⅷ collagen(col8al),and connective tissue growth factor(ctgf).Western blot(n=3)was performed to verify the protein expression levels of α-SMA.MI modeling was performed on the WT and the Mydgf-KO mice.Postoperative LVEF and LVFS(n=10)were then measured.The hearts were harvested and Masson staining was performed to determine the infarcted area(n=10).The heart samples of Mydgf-KO and WT mice were collected at d 7 and d 14 after MI,respectively,to verify the expression of myofibroblast markers(n=3).Results Compared with WT mice,LVEF and LVFS in adult Mydgf-KO mice showed no significant changes(all P＞0.05).However,the mRNA levels of α-SMA and postn were upregulated,and α-SMA protein expression was also increased(all P＜0.05).After MI,compared with WT mice,LVEF and LVFS in Mydgf-KO mice decreased,and the infarcted area increased significantly(all P＜0.05).Furthermore,mRNA levels of α-SMA,col8al,postn,and ctgf were increased in Mydgf-KO mice.In addition,the α-SMA protein expression level was upregulated and α-SMA-positive fibroblasts were increased(P＜0.05).Conclusion Mydgf deletion promotes the transformation of cardiac fibroblasts into myofibroblasts and aggravates myocardial fibrosis after MI.
万方数据
维普
