Glucose impairs angiogenesis and promotes ventricular remodelling following myocardial infarction via upregulation of microRNA-17

• Published in: Experimental cell research Vol. 381; no. 2; pp. 191 - 200
• Main Authors: Yan, Meiling, Chen, Kankai, Sun, Rong, Lin, Kaibin, Qian, Xiaolin, Yuan, Minjie, Wang, Yanpeng, Ma, Jian, Qing, Yanwei, Xu, Jun, Wei, Meng, Huang, Dong, Li, Jingbo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2019
• Subjects: Angiogenesis; Diabetes; MicroRNA-17; Myocardial infarction; Myocardial infarction; Angiogenesis; MicroRNA-17; Diabetes
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2019.04.039

Hyperglycaemia is known to impair angiogenesis, which may contribute to the poor prognosis of diabetic patients following myocardial infarction (MI). miR-17 has been reported to be involved in the proliferation, migration, and angiogenesis of a variety of vascular endothelial cells. However, how miR-17 regulates angiogenesis under hyperglycaemic conditions has not been reported. Thus, the aim of this study was to investigate the role of miR-17 in the impairment of angiogenesis induced by high glucose. In vitro, human umbilical vein endothelial cells (HUVECs) transfected with miR-17 mimics or inhibitors were incubated with normal-glucose or high-glucose (HG) medium. In vivo, miR-17 or negative control antagomirs were administered by tail vein injection in an MI model of streptozotocin (STZ)-induced diabetic mice. MiR-17 was upregulated, while VEGFA was downregulated in MI mice with diabetes and in HUVECs exposed to HG. The luciferase reporter gene assay confirmed that VEGFA is a target gene of miR-17. Moreover, inhibition of miR-17 prevented HG-induced VEGFA downregulation and impaired the capacity for migration and tube formation in HUVECs. Administration of miR-17 antagomirs significantly improved LV function and reduced infarct size in diabetic post-MI mice. Furthermore, the effects of diabetes-induced decreases in angiogenesis and VEGFA expression were abrogated by miR-17 antagomirs treatment in diabetic infarcted myocardium. These findings suggest that inhibition of miR-17 prevents HG-induced impairment of angiogenesis and improves cardiac function after MI by targeting VEGFA in diabetic mice. •miR-17 negatively regulated VEGFA expression in vitro and in vivo.•Inhibition of miR-17 prevented HG-induced impairment of angiogenesis.•Inhibition of miR-17 reduces ventricular remodelling following MI in diabetic mice.