Flow Sensitive Genes in Endothelial Inflammation and Atherosclerosis - OMICs Approaches and Nanomedicine

Abstract

Atherosclerosis is the major underlying cause of myocardial infarction and stroke and preferentially occurs in arterial regions exposed to disturbed flow (d-flow) by mechanisms involving broad changes in gene expression. We have shown that D-flow rapidly induces atherosclerosis in vivo using a mouse partial carotid ligation model. In addition, we developed a novel intimal RNA/DNA preparation method using this animal model and identified numerous mechanosensitive endothelial genes and epigenetic DNA methylome that change in response to d-flow. We showed that flow robustly regulate expression of microRNAs, including miR-712/205 family and miR-663, and their roles in endothelial inflammation and atherosclerosis. Our results showed that targeting mechanosensitive “athero-miRs” with anti-miR-based approaches may provide a new treatment paradigm in atherosclerosis. We also showed recently that these anti-miRs can be delivered to inflamed endothelium in vivo by using the VCAM1-targeting nanoparticle to treat atherosclerosis in mouse. These flow-sensitive novel anti-atherogenic therapeutics and their targeted delivery using nanoparticles are exciting future directions in prevention and treatment of atherosclerotic diseases.