MicroRNAs in vascular smooth muscle cells: Mechanisms, therapeutic potential, and advances in delivery systems.

Vascular smooth muscle cells (VSMCs) are essential players in a wide range of physiological processes, and their phenotypic transitions are critical in the development of vascular diseases such as atherosclerosis (AS), restenosis, aortic dissection/aneurysm (AAD), chronic kidney disease (CKD), and diabetes mellitus (DM). MicroRNAs (miRNAs), a class of short non-coding RNAs, regulates key cellular functions like proliferation, migration, and apoptosis by modulating gene expression. Numerous studies have shown that various miRNAs play pivotal roles in the pathophysiological processes of VSMCs, with VSMC phenotype switching being a key factor. To harness miRNAs as therapeutic tools, researchers have focused on developing efficient delivery vectors, including exosomes, nanoparticles, and viral vectors. Recently, the exploration of miRNA characteristics and delivery mechanisms has led to the emergence of innovative systems, such as scaffold-based localized delivery methods, platelet-like fusion lipid nanoparticles(PLPs), liposome-exosome hybrid carriers, and stimulus-responsive delivery systems like miRNA micelles. These cutting-edge delivery systems not only enhance our understanding of miRNA's role in disease but also offer promising new strategies for gene therapy, paving the way for more precise and effective treatments in the future.