Role and mechanism of miR‑222‑5p in endothelial cell apoptosis

Atherosclerosis (AS) is a chronic, multifactorial condition strongly associated with the onset and progression of cardiovascular disease, and it remains one of the leading causes of mortality worldwide. Endothelial cell apoptosis is an important event in the initiation and development of AS. MicroRNAs (miRNAs/miRs) have been extensively studied and perform roles at various stages of AS. Among them, miR‑222‑5p has been implicated in the regulation of AS; however, its precise mechanistic involvement remains to be fully elucidated. Therefore, the present study aimed to determine the functional role and underlying mechanism of miR‑222‑5p in AS. To this end, human umbilical vein endothelial cells (HUVECs) were treated with oxidized low‑density lipoprotein (ox‑LDL) to establish an endothelial cell apoptosis model. Reverse transcription‑quantitative polymerase chain reaction was used to assess mRNA and miRNA levels, and transfection efficiency. Cell viability was measured using the Cell Counting Kit‑8 assay and apoptosis was determined by flow cytometry. The protein expression levels of Bax, Bcl‑2 and integrin subunit α5 (ITGA5) were determined by western blotting. The results revealed that ox‑LDL stimulation significantly increased miR‑222‑5p expression in HUVECs. Overexpression of miR‑222‑5p significantly promoted apoptosis, whereas its knockdown reduced apoptosis and improved cell viability. Further analysis identified ITGA5 as a potential downstream target of miR‑222‑5p. In ox‑LDL‑induced apoptosis models, ITGA5 expression was significantly downregulated, and transfection with small interfering RNA targeting ITGA5 (si‑ITGA5) enhanced apoptotic activity. Furthermore, an inverse relationship was observed between ITGA5 and miR‑222‑5p expression. Co‑transfection experiments revealed that si‑ITGA5 partially reversed the anti‑apoptotic effects of the miR‑222‑5p inhibitor. In summary, the present study demonstrated that miR‑222‑5p may regulate endothelial cell apoptosis by targeting ITGA5, potentially contributing to AS progression.