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Research Paper|Volume 14, Issue 7|pp 3129—3142

miRNA-29 aggravates myocardial infarction via inhibiting the PI3K/mTOR/HIF1α/VEGF pathway

Xiaoxi Wang1, Yanning Liu2, Huiqing Hou3, Weihua Shao4, Dai Huang5, Zhihua Hao3, Hongyuan Xue5, Yuquan Ye6
  • 1Department of Medical Examination Center, Hebei Medical University, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
  • 2Department of Neurosurgery, 980 Hospital of PLA Joint Logistics Support Forces, Shijiazhuang 050051, Hebei, China
  • 3Medical Examination Center, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
  • 4Department of Second Division of Geriatrics, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
  • 5Department of Medical Imaging and Ultrasound, Hebei Medical University, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
  • 6Ultrasound Department, Hebei Medical University, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
Received: June 18, 2021Accepted: February 28, 2022Published: April 4, 2022
https://doi.org/10.18632/aging.203997

Copyright: © 2022 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Introduction: MI is defined by the presence of myocardial necrosis, which is caused by acute and persistent ischemia and hypoxia of the coronary artery. In recent years, its incidence rate has been on the rise in China.

Methods: GSE34198, GSE97320 and GSE141512 datasets were download for DEG analysis. KEGG pathway analysis, GO analysis, GSEA and PPI network construction were performed. Later, target genes of candidate miRNAs were predicted. Next, echocardiography was conducted to detect the effects of miR-29 on left ventricular structure and cardiac function in vivo, and H&E staining was adopted to study the effects of miR-29 on angiogenesis and fibrosis in vivo. Furthermore, Western blotting was employed to investigate the effects of miR-29 inhibition on the expressions of proteins related to the PI3K\mTOR\ HIF-1α\VEGF pathway.

Results: There were 162 DEGs involved in MI. GO analysis revealed that inflammatory responses, negative regulation of apoptosis and innate immune response were the main enriched biological processes. KEGG analysis manifested that DEGs were mainly enriched in the PI3K/Akt signaling pathway, and GSEA demonstrated that they were mainly enriched in the PI3K/Akt/mTOR, HIF and VEGF pathways. Moreover, target gene prediction showed that miR-29 was lowly expressed in MI. According to Masson's trichrome staining, miR-29 inhibition promoted angiogenesis, reduced fibrosis, and increased the protein expressions of p-PI3K, p-mTOR, HIF-1α, and VEGF.

Conclusions: MiR-29 may play an important role in the growth and development of MI. After inhibition of miR-29, the PI3K/mTOR/HIF-1α/VEGF pathway is activated to alleviate MI.