MiR-590-3p Promotes the Phenotypic Switching of Vascular Smooth Muscle Cells by Targeting Lysyl Oxidase

Abstract

We investigated the clinical characteristics of patients with acute aortic dissection (AAD) and miR-590-3p levels in serum, tissue, and vascular smooth muscle cells (VSMCs). The effect of miR-590-3p on the VSMC phenotype was assessed, and the regulation of lysyl oxidase (LOX) by miR-590-3p was determined. C57BL/6 mice were used to investigate the incidence of AAD and effects of miR-590-3p on AAD. MiR-590-3p levels were measured in the aortae of mice, and hematoxylin and eosin (H&E) staining and Masson staining were performed to identify the morphological features of the aorta. Comparative analysis revealed significant differences in clinical characteristics between AAD patients and healthy controls, with most patients with AAD exhibiting concomitant hypertension and nearly 50% having atherosclerosis. LOX was a direct target of miR-590-3p. LOX overexpression inhibited switching of the VSMC phenotype from contractile to synthetic, but miR-590-3p overexpression significantly reversed this change. In the mouse model, miR-590-3p upregulation increased the incidence of AAD to 93.3%, and its incidence decreased to 13.3% following miR-590-3p inhibition. H&E and Masson staining revealed that the miR-590-3p agomiR group had a greater loss of the contractile phenotype in the dissected aortic wall and an increased number of muscle fibers in the aortic wall, which contributed to thickening of the aortic wall and the formation of a false lumen in AD. miR-590-3p might be pivotal in the pathogenesis of AAD. Thus, targeting miR-590-3p or its downstream pathways could represent a therapeutic approach for AAD.