MiR-145-5p alleviates hypoxia/reoxygenation- induced cardiac microvascular endothelial cell injury in coronary heart disease by inhibiting Smad4 expression

Objective: To investigate the effects and mechanism of miR-145-5p on hypoxia/reoxygenation (H/R)-induced cardiac microvascular endothelial cell (CMEC) injury in coronary heart disease (CHD).

Patients and methods: Patients with CHD (n=96) and healthy volunteers (n=96) were enrolled, and H/R injury model of CMECs was established. The expression of miR-145-5p and mothers against decapentaplegic homolog 4 (Smad4) mRNA in cells was quantified with reverse transcription polymerase chain reaction (RT-PCR). Then, miR-145-5p mimics and Smad4 inhibitor were transfected into CMECs. Cell counting kit-8 (CCK-8) was employed for proliferation detection, flow cytometry for apoptosis detection, and Western Blot for measuring the expression of apoptosis-related proteins and Smad4 protein.

Results: The expression of serum miR-145-5p in patients with CHD was significantly lower than that in healthy individuals. The area under the curve (AUC) of miR-145-5p in diagnosing CHD was 0.894, and the expression of miR-145-5p was negatively correlated with that of Smad4 (p<0.05). Over-expression of miR-145-5p promoted the proliferation, inhibited the apoptosis, and reduced inflammatory responses and oxidative stress in H/R-injured CMECs. Moreover, miR-145-5p might negatively regulate the expression of Smad4 in CMECs. Dual-Luciferase reporter assay determined the targeting relation between miR-145-5p and Smad4.

Conclusions: MiR-145-5p is lowly expressed in patients with CHD, and its over-expression effectively alleviates H/R-induced CMEC injury by inhibiting Smad4.