Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 120, Issue 2, Pages 1598-1609Publisher
WILEY
DOI: 10.1002/jcb.27433
Keywords
angiogenesis; apoptosis; capillary-like structures; cardiac microvascular endothelial cell; inflammatory injury; microRNA-34a; Notch signaling pathway
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ObjectiveRecently, microRNA-34a (miR-34a) has been reported to lead to secretion of proinflammatory cytokine in endothelial cells, whereas whether miR-34a plays a protective role in damaged cardiac microvascular endothelial cells (CMECs) remains to be determined. Herein, the purpose of this study is to explore the effect of miR-34a in mediating Notch signaling pathway in apoptosis and angiogenesis of damaged CMECs. MethodsThe primary mice CMECs were isolated, cultivated, and identified before establishment of damaged CMEC model by incubation with homocysteine (HCY) for 24hours. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were applied to determine the expressions of miR-34a and Notch1. Cell viability and cell apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Hochest 33258 staining. Capillary-like structures formation assay was used to detect the capillary-like structures in CMECs. The expressions of inflammatory cytokines and angiogenesis factors were determined by enzyme-linked immunosorbent assay. ResultsIn contrast to the blank group, the HCY and negative control groups demonstrated with elevated expressions of miR-34a, interleukin (IL)-1, IL-6, and increased cell apoptosis rate, but decreased expressions of Notch1, IL-10, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and human growth factor (HGF), as well as attenuated cell viability and capillary-like structures of cells formation ability. In comparison with HCY group, the expressions of miR-34a, IL-1, IL-6, and apoptosis rate were increased, whereas the expressions of Notch1, VEGF, bFGF, HGF, cell viability, and capillary-like structures of cells formation were inhibited in miR-34a mimic group. ConclusionThis study demonstrates that miR-34a can promote CMEC apoptosis and upregulate inflammatory cytokines, thus worsening CMEC damage and inhibiting angiogenesis by negatively targeting the Notch signaling pathway.
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