Inhibition of AZIN2-sv induces neovascularization and improves prognosis after myocardial infarction by blocking ubiquitin-dependent talin1 degradation and activating the Akt pathway

摘要: Abstract Background We previously found that loss of lncRNA-AZIN2 splice variant (AZIN2-sv) increases cardiomyocyte (CM) proliferation and attenuates adverse ventricular remodelling post-myocardial infarction (MI). However, whether inhibition AZIN2-sv can simultaneously induce angiogenesis thus improve prognosis after MI is unclear. Methods used in situ hybridization quantitative PCR to determine expression endothelial cells. Knockdown overexpression were performed detect the role cell function, MI. RNA pulldown, immunoprecipitation luciferase reporter assays interaction with talin1 (Tln1) protein miRNA-214 (miR-214). DNA pulldown chromatin (ChIP) study binding upstream transcription factors. Findings was enriched cardiac The reduced apoptosis promoted sprouting capillary network formation vitro. Moreover, vivo, induced improved function Mechanistically, Tln1 integrin β1 (ITGB1) levels inhibit neovascularization. activated ubiquitination-dependent degradation mediated by proteasome 26S subunit ATPase 5 (PSMC5). In addition, could bind miR-214 suppress phosphatase tensin homologue (PTEN)/Akt pathway angiogenesis. With regard mechanism, Bach1, a negative regulator angiogenesis, bound promoter increased its expression. Interpretation Bach1-activated participate promoting PSMC5-mediated blocking miR-214/PTEN/Akt pathway. Inhibition myocardial regeneration simultaneously, thus, be an ideal therapeutic target for improving repair Fund National Natural Science Foundations China.