MiR-518a-5p Targets GZMB to Extenuate Vascular Endothelial Cell Injury Induced by Hypoxia-Reoxygenation and Thereby Improves Myocardial Ischemia

Abstract

To probe the function of miR-518a-5p/Granzyme B (GZMB) in hypoxia/reoxygenation (H/R)-induced vascular endothelial cell injury.The key genes of myocardial infarction were screened by bioinformatic methods. The upstream micro RNAs (miRNAs) of GZMB were predicted by TargetScan. The binding of miR-518a-5p to GZMB was verified with luciferase reporter assay. The H/R model was constructed with human vascular endothelial cell (HUVEC) in vitro. Cell Counting Kit-8 (CCK8) assay was performed to detect cell proliferation. Western blot was utilized to evaluate the levels of indicated proteins.GZMB was up-regulated in patients with myocardial infarction and identified as the key gene by the bioinformatics analysis. Then the prediction from TargetScan indicated that miR-518a-5p, which is down-regulated in myocardial infarction patients, might be the potential upstream miRNA for GZMB. The following experiments verified that miR-518a-5p could bind to the 3'UTR of GZMB and negatively modulates GZMB expression. More importantly, the miR-518a-5p mimic enhanced cell proliferation and repressed apoptosis of H/R-injured HUVEC cells by inhibiting GZMB expression.We proved that miR-518a-5p could partly attenuate H/R-induced HUVEC cell injury by targeting GZMB, and perhaps the miR-518a-5p/GZMB axis could be potential therapeutic targets for myocardial infarction.

MicroRNAs Expression Profile in Young Patients with Acute Myocardial Infarction

“…Other miRNAs that suppress apoptosis in cardiomyocytes are miR-431, 518a-5p, and miR-105, by targeting autophagy-relate 3 (ATG3), Granzyme B (GZMB), RIP3, and BNIP3 respectively. 29,41,47 The downregulation of miR-431, miR-518, and miR-105 in Young AMI against Mature AMI patients in our study, suggest that age factor may lead to differential expression of these miRNAs.…”

Predicting diagnostic gene Biomarkers associated with N6-methyladenosine and ferroptosis in patients with acute myocardial infarction

“…Granase B (GZMB), a member of the serine protease family of granase, promotes apoptosis and is currently the most widely studied granase in the eld of health and disease [46]. Studies have shown that mir-518a-5p can target GZMB to reduce hypoxia-reoxygenation-induced vascular endothelial cell injury, thereby improving coronary artery disease [47]. GZMK, belonging to the granase serine protein family, also plays a key role in myocardial ischaemia.…”

Programmed Cell Death of Endothelial Cells in Myocardial Infarction and Its Potential Therapeutic Strategy

“…MiR-124 induces ECs apoptosis via the P38/MAPK and PI3K/AKT pathways and may be a contributing factor in vascular endothelial damage in AMI [ 43 ]. By targeting granzyme B, MiR-518a-5p can reduce hypoxia/reoxygenation (H/R)-induced apoptosis and cell damage in human umbilical vein endothelial cells (HUVECs) [ 44 ].…”