miR‑124 promotes apoptosis and inhibits the proliferation of vessel endothelial cells through P38/MAPK and PI3K/AKT pathways, making it a potential mechanism of vessel endothelial injury in acute myocardial infarction

Abstract

Due to its rapid onset and high rates of fatality, acute myocardial infarction (AMI) has long been one of the most fatal diseases among all types of heart diseases. Therefore, intensive research efforts have been focused on understanding AMI's potential pathogenesis to seek effective treatment options. In the present study, 20 peripheral blood samples were collected from patients with AMI, after which reverse transcription-quantitative PCR analysis revealed that microRNA (miR)-124 levels in the peripheral blood of patients with AMI was significantly elevated compared with that in the control group. In vitro , a model using pcDNA3.1-miR-124 transfected human umbilical vein endothelial cells (HUVECs) indicated that overexpression of miR-124 could significantly promote the apoptosis and suppress the proliferation of HUVECs using flow cytometry, TUNEL assay and Cell Counting Kit-8 assays. Based on the present findings, RNA samples of HUVECs overexpressing miR-124 was extracted and sequenced to explore the gene expression profile after miR-124 overexpression. Gene Set Enrichment Analysis (GSEA) analysis revealed that the downregulated genes were mainly enriched in signaling pathways, such as PI3K-AKT, whilst the upregulated genes were mainly enriched in metabolism-related signaling pathways, such as the metabolism of xenobiotics by cytochrome P450 pathway. Additionally, Rideogram software was used to determine the chromosomal localization of the differentially expressed genes. The results demonstrated that they were distributed on all chromosomes except for chromosome Y. In addition, characteristic profiles of the differentially expressed genes caused by miR-124 overexpression were analyzed using Connectivity Map. In total, two medicines, anisomycin and sanguinarine, which function as p38/MAPK signaling agonists that can inhibit angiogenesis, presented with the highest enrichment scores. Together with the GSEA results, which indicated that the differentially expressed genes were mainly enriched in the angiogenesis-inhibiting PI3K/AKT signaling pathway, the present study reported that high expression of miR-124 was negatively associated with patients with AMI, promoting the apoptosis and suppressing the proliferation of vessel endothelial cells.

Response surface optimization of a cardioprotective compound through pharmacosomal drug delivery system: in vivo bioavailability and cardioprotective activity potential

“…12). As stated earlier, the intracellular signaling pathways MAPK and PI3K/AKT/NF-κB affect myocardial infarction [60][61][62]. It was observed that VA treated group showed a significant reduction in the expression levels of AKT in heart tissue as compared to the isoprenaline control group, with a subsequent inhibition of the myocardial contents of the proinflammatory mediators IL-6.…”

“…Previous studies have demonstrated the involvement of stimulation of mitogen-activated protein kinase (MAPK) in the pathogenesis of myocardial cell degeneration and infarction [58,59]. The intracellular signaling pathways MAPK and PI3K/AKT/NF-κB were demonstrated to be vital in both regulating inflammatory mediators and cell structure alterations in a sequential cascade manner in many diseases including myocardial infarction [60][61][62]. In comparison to the isoprenaline control group, treatment with VA revealed a significant reduction in the expression levels of MAPK and PI3K, in heart tissue.…”

MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis

“…Our findings further suggest that miR-497-5p exacerbates ox-LDL-induced HUVEC damage and activates the p38 MAPK pathway. Comparable studies show miR-124 involvement in vessel endothelial cell apoptosis and proliferation inhibition via the p38/MAPK pathway [ 38 ]. Consequently, we hypothesize that the MAPK pathway contributes to the increased apoptosis, inflammation, and oxidative stress in ox-LDL-stimulated endothelial cells, influenced by miR-497-5p.…”

Sensitive fluorescence detection of miRNA-124 in cardiomyocytes under oxidative stress using a nucleic acid probe

“…The latest studies found that miR-124 levels are significantly increased when AMI occurs, and miR-124 is strongly expressed in all smoking individuals and is associated with the risk of subclinical arteriosclerosis caused by related increases in altered single-cell phenotypes [ 22 ]. The median level of relative expression of miR-124 in the blood of patients with acute myocardial infarction is about 1.5 times of that in normal people [ 23 ]. Randomized clinical trials have shown that serum miR-124 levels may be a useful prognostic indicator of the outcome after cardiac arrest [ 24 ].…”