Effects of mir-21 on Cardiac Microvascular Endothelial Cells After Acute Myocardial Infarction in Rats: Role of Phosphatase and Tensin Homolog (PTEN)/Vascular Endothelial Growth Factor (VEGF) Signal Pathway
Feng Yang, Wenwei Liu, Xiaojuan Yan, Hanyun Zhou, Hongshen Zhang, Jianfei Liu, Ming Yu, Xiaoshan Zhu, Kezhong Ma
Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China (mainland)
Med Sci Monit 2016; 22:3562-3575
This study investigated how miR-21 expression is reflected in acute myocardial infarction and explored the role of miR-21 and the PTEN/VEGF signaling pathway in cardiac microvascular endothelial cells.
MATERIAL AND METHODS: We used an in vivo LAD rat model to simulate acute myocardial infarction. MiR-21 mimics and miR-21 inhibitors were injected and transfected into model rats in order to alter miR-21 expression. Cardiac functions were evaluated using echocardiographic measurement, ELISA, and Masson staining. In addition, lenti-PTEN and VEGF siRNA were transfected into CMEC cells using standard procedures for assessing the effect of PTEN and VEGE on cell proliferation, apoptosis, and angiogenesis. MiR-21, PTEN, and VEGF expressions were examined by RT-PCR and Western blot. The relationship between miR-21 and PTEN was determined by the luciferase activity assay.
RESULTS: We demonstrated that miR-21 bonded with the 3’-UTR of PTEN and suppressed PTEN expressions. Established models significantly induced cardiac infarct volume and endothelial injury marker expressions as well as miR-21 and PTEN expressions (P<0.05). MiR-21 mimics exhibited significantly protective effects since they down-regulated both infarction size and injury marker expressions by increasing VEGF expression and inhibiting PTEN expression (P<0.05). In addition, results from in vitro research show that lenti-PTEN and VEGF siRNA can notably antagonize the effect of miR-21 on cell proliferation, apoptosis, and angiogenesis (P<0.05).
CONCLUSIONS: MiR-21 exerts protective effects on endothelial injury through the PTEN/VEGF pathway after acute myocardial infarction.
Keywords: Apoptosis - genetics, Animals, Angiogenesis Inhibitors - metabolism, 3' Untranslated Regions, Cell Proliferation - genetics, Endothelial Cells - pathology, mesenchymal stromal cells, MicroRNAs - metabolism, Microvessels - pathology, Myocardial Infarction - pathology, Neovascularization, Pathologic - pathology, PTEN Phosphohydrolase - metabolism, RNA, Small Interfering - genetics, Rats, Rats, Sprague-Dawley, Signal Transduction, Tensins - metabolism, Vascular Endothelial Growth Factor A - metabolism