Role of Carvedilol in Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells by Upregulating microRNA-145 Expression

The proliferation and migration of vascular smooth muscle cells (VSMCs) are the initial contributors to restenosis in patients undergoing percutaneous coronary intervention (PCI). MicroRNA-145 (miR-145) plays a significant role in this pathological process. Although carvedilol has been shown to inhibit VSMC proliferation and migration, the underlying mechanisms are not fully understood. The aim of our study is to examine whether carvedilol regulates the expression of miR-145 and thereby inhibits the proliferation and migrative capacity of VSMCs. VSMCs were cultured and transfected with either miR-145 mimics or miR-145 inhibitors. Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2?-deoxyuridine (EdU) assays, while wound healing and Transwell assays were used to assess the migration capacity. Protein expression levels were quantified using western blot analysis, and additionally, a luciferase reporter assay was performed to identify the target gene of miR-145. We found that carvedilol upregulated the expression of miR-145 and decreased the expression of Krüppel-like factor 4 (KLF4). Furthermore, miR-145 inhibited VSMC proliferation and migration. KLF4 was identified as a direct target of miR-145. Importantly, the inhibition of miR-145 attenuated the suppressive effects of carvedilol on VSMCs. In summary, our results in this study demonstrate that carvedilol exerts its inhibitory effects on VSMC proliferation and migration, at least in part, through the upregulation of miR-145. These findings suggest that miR-145 may be a key mediator in the therapeutic effects of carvedilol on VSMCs.