Abstract
Coronary microembolization (CME) is an intractable complication results from acute coronary syndrome. CME-induced myocardial apoptosis was associated with progressive cardiac contractile dysfunction. miR-29b-3p has been reported implicated in variety cardiovascular diseases, but its function in CME-induced myocardial injury is yet unknown. Herein, a rat model of CME was established by injecting microspheres into the left ventricle and found that the expression level of miR-29b-3p was markedly decreased in the CME rat heart tissues. By using echocardiography, CD31 immunohistochemistry staining, hematoxylin basic fuchsin picric acid (HBFP) staining, TUNEL staining, and western blotting analysis after CME, it was found that upregulating miR-29b-3p improved cardiac dysfunction, promoted angiogenesis, decreased myocardial microinfarct area, and inhibited myocardial apoptosis. Additionally, miR-29b-3p inhibition can reverse the protective benefits of miR-29b-3p overexpression. Mechanistically, the target genes of miR-29b-3p were identified as glycogen synthase kinase 3 (GSK-3β) and Bcl-2 modifying factor (BMF) by bioinformatics analysis and luciferase reporter experiment. Overall, our findings imply that induction of miR-29b-3p, which negatively regulates GSK-3β and BMF expression, attenuates CME-induced myocardial injury, suggesting a novel potential therapeutic target for cardioprotective after CME.
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The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was supported from the Project for Innovative Research Team in Guangxi Natural Science Foundation (No. 2018GXNSFGA281006), National Nature Science Foundation of China (No. 82170349, No. 81900318), and Guangxi Natural Science Foundation (No. 2018GXNSFBA050017).
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LL and XW conceived the project and designed experiments. ZQ, XW, YZ, JZ and HL performed the experiments. ZQ and XW analyzed the data. ZQ and LL wrote the manuscript.
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Qin, Z., Wang, X., Zhou, Y. et al. Upregulation of miR-29b-3p alleviates coronary microembolization-induced myocardial injury via regulating BMF and GSK-3β. Apoptosis 28, 210–221 (2023). https://doi.org/10.1007/s10495-022-01788-z
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DOI: https://doi.org/10.1007/s10495-022-01788-z