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

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.

Desoxyrhaponticin attenuates M1 Macrophage Polarization via targeting PI3K/AKT/mTOR signaling pathway in RAW264.7 macrophage cells

“…All of these suggesting that AKT molecule converges multiple signals to regulate macrophage pro-and antiin ammatory effects. The role of PI3K/AKT/mTOR signaling pathway in myocardial infarction including regulation of macrophage phenotypic transformation [25], autophagy [26] and angiogenesis [27]. Our results investigated that Desoxyrhaponticin inhibited macrophages M1 polarization by downregulating PI3K/AKT/mTOR signaling pathway.…”

miRNA Dysregulation in Cardiovascular Diseases: Current Opinion and Future Perspectives

“…Wang et al [ 44 ] investigated the role of miR-22 and miR-499 as sensitive biomarkers in the diagnosis of MI, confirming that these miRNAs could play an important role in early diagnosis. Wang et al [ 77 ] investigated the role of miR-29: it was expressed less in subjects after MI. These authors demonstrated that the inhibition of this miRNA promoted angiogenesis, reduced fibrosis, and alleviated MI damage.…”

Advances in Hypoxia-Inducible Factor 1-Alpha and Ischemic Heart Disease

“…In addition, polarization of HAE may also play a protective role through VEGF induction of angiogenesis. Wang et al [16] also show that injection of muscone in mice increases angiogenesis around the infarct area, as well as increased phosphorylated VEGF Receptor (P-VEGFR2) in vascular endothelial cells. Western blot and PCR results show increased expression of HIF-1α and VEGF, which proves that muscone can protect myocardial infarction by up-regulating VEGF through HIF-1α.…”

“…miR-29 works by increasing the contractile load of cardiac myocytes and results in more serious disease, and it can combine with PI3K so that, it can initiate the phosphorylation pathway which leads to PI3K to degrade. In other words, after the use of inhibitors, PI3K/mTOR/HIF-1α/VEGF pathway can be activated and the increase of the VEGF expression promotes and improves the function of myocardial cell [16] . Gonzalez-king et al [15] show that injection of Hydroxyapatite Electret (HAE) into mice can significantly reduce myocardial infarction area and fibrosis in the distal unaffected area is also significantly reduced.…”