Inhibition of myocardial remodeling through miR-150/TET3 axis after AMI

  • Impact factors: 2.8
  • Publication: MOLECULAR BIOLOGY REPORTS
  • Author:Lu Wenbin, Liu Zhuyuan, Chiara Villamil Orion I. R., Qu Yangyang, Ma Genshan
  • DOI citation-doi:10.1007/s11033-023-08932-1
  • Date:2023-12-28

Background Current studies have suggested that miRNA is beneficial in inhibiting myocardial remodeling after myocardial infarction (AMI), however, its underlying mechanism is unclear. Objectives We aimed to investigate whether miR-150 can inhibit myocardial remodeling after myocardial infarction and whether this process is regulated by the miR-150/TET3 pathway. Methods On the first day, C57BL/6 AMI mice(n = 15) were administrated with miR-150, and another 15 AMI mice were administrated with the same volume of control Agomir. Left ventricular ejection fraction (LVEF%) and myocardial remodeling were compared after one week; TET3 (ten-eleven translocation 3) and VEGF-α (vascular endothelial growth factor-α) were also determined in the infracted heart simultaneously. The neovascularization in the infarcted area at day 21 was compared through CD31 using fluorescence microscopy; Activated monocytes stimulated with LPS were transfected with miR-150. Laser scanning confocal microscopy was used to detect the intracytoplasmic imaging of miR-150 in Ly6C high monocytes. Expression of the miR-150 in the monocytes was measured using Q-PCR. After 48 h, the proportion of Ly6C high/low monocytes was determined using flow cytometry. Expression of TET3 in Ly6C high/low monocytes was measured using Q-PCR and Western blot. After the downregulation of TET3 specifically, the levels of Ly6C high/low monocytes were further determined. Results We first observed an increased trend of mice survival rate in the miR-150 injection group, but it didn’t reach a statistical difference (66.7% vs. 40.0%, p = 0.272). However, AMI mice administrated with miR-150 displayed better LVEF% (51.78%±2.90% vs. 40.28%±4.20%, p<0.001) and decreased infarct size% (25.47 ± 7.75 vs. 50.39 ± 16.91, p = 0.002). After miR-150 was transfected into monocytes, the percentage of Ly6C low monocytes increased significantly after 48 h (48.5%±10.1% vs. 42.5%±8.3%, p < 0.001). Finally, Western blot analysis (0.56 ± 0.10/β-actin vs. 0.99 ± 0.12/β-actin, p < 0.001) and real-time PCR (1.09 ± 0.09/GAPDH vs. 2.53 ± 0.15/GAPDH, p < 0.001, p < 0.001) both confirmed decreased expression of TET3 in monocytes after transfection with miR-150. After the downregulation of TET3 specifically, Ly6C low monocytes showed a significant increase (16.73%±6.45% vs. 6.94%±2.99%, p<0.001, p < 0.001). Conclusions miR-150 alleviated myocardial remodeling after AMI. Possible mechanisms are ascribed to the regulating of TET3 and VEGF-α in inflammatory monocytes.

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