MicroRNA-16-5p Aggravates Myocardial Infarction Injury by Targeting the Expression of Insulin Receptor Substrates 1 and Mediating Myocardial Apoptosis and Angiogenesis

(E-pub Ahead of Print)

Author(s): Xiancan Wang, Yuqiang Shang*, Shilin Dai, Wei Wu, Fan Yi, Long Cheng.

Journal Name: Current Neurovascular Research

Become EABM
Become Reviewer


Purpose: Myocardial infarction is a common cardiovascular disease. miR-16-5p was upregulated in heart and kidney hypoxia/reoxygenation (H/R) injuty. However, the role of miR-16-5p in myocardial infarction injury is still unclear.

Methods: Human adult ventricular cardiomyocytes (AC16) were treated with ischemia/reperfusion (H/R). miR-16-5p level was evaluated through real-time PCR. The activity of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) was detected via according kits. Cell viability was examine with 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay. Western blotting was used to analyzed the protein levels. The luciferase report assay confirmed the relative lucifierase activity.

Results: miR-16-5p was elevated in H/R-treated AC16 cells. miR-16-5p overexpression and knockdown were carried out. miR-16-5p knockdown repressed cell apoptosis, attenuated LDH and CK-MB activities, and enhanced cell viability in H/R-treated AC16 cells. Moreover, miR-16-5p knockdown promoted angiogenesis in human microvascular endothelial cells (HMVEC), causing elevation of vascular endothelial growth factor (VEGF), insulin receptor substrates 1 (IRS1), minichromosome maintenance complex component 2 (MCM2) and proliferating cell nuclear antigen (PCNA)MCM2 protein levels. Moreover, miR-16-5p was testified to target IRS1. IRS1 silencing alleviated miR-16-5p knockdown-mediated inhibition of apoptosis in AC16 cells.

Conclusion: miR-16-5p knockdown increased cell viability and angiogenesis, as well as inhibit cell poptosis via increasing IRS1. These findings indicated that miR-16-5p knockdown may be a new therapeutic target for myocardial infarction.

Keywords: miR-16-5p, IRS1, Apoptosis, Angiogenesis, Myocardial infarction, Vascular endothelial growth factor

Rights & PermissionsPrintExport Cite as

Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1567202617666191223142743
Price: $95

Article Metrics

PDF: 1