Delivery of miR-654-5p via SonoVue Microbubble Ultrasound Inhibits Proliferation, Migration, and Invasion of Vascular Smooth Muscle Cells and Arterial Thrombosis and Stenosis through Targeting TCF21.

ABSTRACT

Background: Abnormal proliferation of vascular smooth muscle cells (VSMCs) is an important cause of vascular stenosis. The study explored the mechanism of inhibition of vascular stenosis through the molecular mechanism of smooth muscle cell phenotype transformation. Methods: Coronary heart disease-related genes were screened by bioinformatics, and the target genes of miR-654-5p were predicted by dual-luciferase method and immunofluorescence method. miR-654-5p mimic stimulation and transfection of TCF21 and MTAP into cells. SonoVue microbubble sonication was used to deliver miR-654-5p into cells. Cell proliferation, migration, and invasion were detected by CCK-8, wound scratch, and Transwell. HE and IHC staining were performed to study the effect of miR-654-5p delivery via SonoVue microbubble ultrasound on vessel stenosis in a model of arterial injury. Gene expression was determined by qRT-PCR and WB. Results: TCF21 and MTAP were predicted as the target genes of miR-654-5p. Cytokines induced smooth muscle cell proliferation, migration, and invasion and promoted miR-654-5p downregulation; noticeably, downregulated miR-654-5p was positively associated with the cell proliferation and migration. Overexpression of TCF21 promoted proliferation, invasion, and migration, and mimic reversed such effects. miR-654-5p overexpression delivered by SonoVue microbubble ultrasound inhibited proliferation, migration, and invasion of cells. Moreover, in arterial injury model, we found that SonoVue microbubble ultrasound transmitted miR-654-5p into the arterial wall to inhibit arterial thrombosis and stenosis, while TCF21 was inhibited. Conclusion: Ultrasound delivery of miR-654-5p via SonoVue microbubbles was able to inhibit arterial thrombosis and stenosis by targeting TCF21.