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| The regulation and mechanism of autophagy on endothelial-to-mensenchymal transition and cardiac fibrosis after acute myocardial infarction |
| Zou Jin, Yang Qin, Li Bin-gong, Ke Xuan, Hao Yan-qin, Li Xue-lian, Li Xing-xing |
| Department of Cardiology, the First Affiliated Hospital, Nanchang University, Nanchang 330006, China |
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Abstract Objective To detect the feasibility of intervening autophagy ameliorates cardiac fibrosis via inhibiting endothelial-to-mesenchymal transition(EndMT) after acute myocardial infarction (AMI). Methods SD rats were randomly divided into 4 groups: Sham group(n=15),AMI group(n=16), AMI+rapamycin group(n=15), and AMI+3-MA group(n=14). Intervening the levels of autophagy by injecting SD rats intraperitoneally after MI. Echocardiography was performed to assess LVEF, LVFS, LVIDd and LVIDs. Masson′s trichrome was performed to assess cardiac fibrosis and collagen volume fraction (CVF) was analyzed. The expressions of CD31, α-SMA, COL1, LC3 and Belin1 in the infarct border zone were examined by Western blot. Double immunofluorescence staining was used to detect the CD31＋α-SMA＋ cells undergoing EndMT and the changes of LC3 in endothelial cells the infarction border zone. Results Compared with the AMI group, rapamycin treatment increased EF and FS, decreased LVIDd, LVIDs and CVF (P<0.05); 3-MA treatment increased CVF (P<0.05), but had no obvious effect on improving cardiac function after myocardial infarction. LC3-II increased significantly within 1 day after AMI, lasting 1～2 days, and then decreased gradually (P<0.05). At the 7th day after AMI, CD31 was downregulated, ɑ-SMA and COL1 were upregulated and the number of CD31+ɑ-SMA+ cells increased in cardiac tissue sections (P<0.05), but LC3 and Beclin1 did not change significantly. Compared with the AMI group, the expression of LC3-II, Beclin1 and CD31 in the AMI+RAP group increased, the expression of ɑ-SMA and COL1 and the number of CD31+ɑ-SMA+ cells decreased (P<0.05). But these treds was reversed in the AMI+ 3-MA group (P<0.05). Conclusion EndMT contributes to cardiac fibrosis post-MI. Enhanced autophagy inhibits EndMT, attenuates cardiac fibrosis and dysfunction.
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Corresponding Authors:
Li Bin-gong, E-mail: libingong08@163.com
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