Enhanced Local Delivery of microRNA-145a-5P into Mouse Aorta via Ultrasound-Targeted Microbubble Destruction Inhibits Atherosclerotic Plaque Formation

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play a key role in the formation and rupture of atherosclerotic plaques. Previous studies have confirmed that microRNA-145 (miR-145) is involved in the phenotypic regulation of VSMCs and reduction of atherosclerosis. At present, seeking safe and effective gene delivery remains a key problem restricting the development of gene therapy. In recent years, ultrasound-targeted microbubble destruction (UTMD) has become a safe and effective transfection method that is widely used in the basic research of gene therapy for heart and tumor diseases. Here, we synthesized cationic microbubbles to encapsulate miR-145 and targeted their release into VSMCs in vitro and in vivo using ultrasound. The feasibility of this gene therapy was verified by fluorescence microscopy and an in vivo imaging system. The results showed that treatment with miR-145 delivered via UTMD considerably improved the gene transfection efficiency and promoted the contraction phenotype of VSMCs in vitro. In vivo, this treatment reduced the atherosclerotic plaque area by 48.04% compared with treatment with free miR-145. Therefore, UTMDmediated miRNA therapy may provide a new targeted therapeutic approach for atherosclerotic plaques.

Automated summary

Abnormal proliferation and migration of VSMCs are crucial in the formation and rupture of atherosclerotic plaques. The use of UTMD for miR-145 delivery significantly improved gene transfection efficiency and promoted the contraction phenotype of VSMCs in vitro. In vivo, this approach reduced the atherosclerotic plaque area compared to free miR-145 treatment.