Abstract Background Neointima formation, a common complication of angioplasty, arises from altered vascular smooth muscle cell (HCASMC) behavior. MicroRNAs (miRs), capable of regulating multiple signaling pathways, have emerged as potential therapeutic targets in cardiovascular diseases. This study explores miR-31-5p as a regulator of HCASMC function to improve vascular healing. Methods C57BL/6J mice (3 months old, male) underwent wire-induced femoral artery injury, with miRNA analysis performed on days 7 and 21 post-injury. qRT-PCR confirmed miR-31-5p expression in human coronary artery endothelial (HCAEC) and smooth muscle cells (HCASMC). RNA sequencing and binding predictions identified miR-31-5p targets, while in vitro studies assessed its effects on migration, proliferation, and apoptosis via lipotransfection. Results Expression analysis revealed a significant upregulation of miR-31-5p (p0.0001) in murine femoral artery neointimal tissue. In vitro, miR-31-5p was significantly upregulated in HCASMC (p0.05) but not HCAEC. On a functional level, miR-31-5p revealed dissenting effects on HCAEC and HCASMC. In HCASMC, miR-31-5p was upregulated (p0.05) and its knockdown reduced migration (p0.01), proliferation (p0.05), and increased apoptosis (p0.05). RNA sequencing identified STK40, LATS2, and GXYLT1 as miR-31-5p targets, validated at mRNA and protein levels. Anti-miR-31-5p transfection significantly downregulated STK40 and LATS2 (p0.01 and p0.05), with no effect in endothelial cells (HCAEC). Further siRNA experiments confirmed that STK40 regulates apoptosis, as its knockdown significantly reduced apoptosis (p0.05) in HCASMC. Importantly, STK40 mediates the pro-apoptotic effects of anti-miR-31-5p (p0.05). Optical analysis localized smoothelin and STK40 within murine aortic cross-sections. Conclusion In summary, miR-31-5p is strongly upregulated during neointima formation, primarily affecting HCASMC by targeting STK40 to induce apoptosis. These findings highlight miR-31-5p as a potential therapeutic target for mitigating HCASMC dysfunction and reducing neointima formation after vascular interventions.
Kalies et al. (Sat,) studied this question.