Microrna-145 Targeted Therapy Reduces Atherosclerosis And Improves Plaque Stability

MicroRNAs are essential post-transcriptional modulators of gene expression that coordinate and integrate multiple regulatory pathways, and have been implicated in various chronic diseases. Since microRNA-145 is highly expressed in vascular smooth muscle cells (VSMCs) and regulates VSMC fate and plasticity, we hypothesized that it may be a novel regulator of atherosclerosis and plaque stability. Atherosclerosis-proneApoE-/- mice were treated with either microRNA-145 lentivirus under the control of the smooth muscle cell-specific promoter SM22α ορ ΣΜ22α χοντρολ λeντιvιρυσ βefορe χομμeνχινγ τηe Ωeστeρν διeτ fορ 12 ωeeκσ. MicroRNA-145 treatment markedly reduced plaque sizes in aortic sinuses, ascending aortas and brachiocephalic arteries. MicroRNA-145 therapy also significantly increased fibrous cap area, reduced the necrotic core area/total plaque area ratio, elevated plaque collagen content, and attenuated MMP-2 and MMP-9 activity. The macrophage content of in plaque areas was significantly decreased in mic...