Abstract 20471: Local Induction of miR21 Increases Fibrous Cap Stability in Vulnerable Atherosclerotic Lesions

Purpose of the current study was to assess the role of miRNAs in fibrous cap stability of advanced atherosclerotic lesions. We used a miRNA-array to analyze laser captured micro-dissected tissue specimen from fibrous caps of 10 symptomatic patients with histo-morphologically identified ruptured lesion vs. fibrous caps from 10 asymptomatic patients with stable lesions. We discovered miR-21 as being most substantially down-regulated in ruptured plaques. To functionally evaluate the contribution of miR-21 to lesion vulnerability, we created Apoe-/-miR21-/- mice (on a C57BL/6 background). In experimental models of vascular remodeling, miR21-/- mice revealed a great lack of smooth muscle cell (SMC) proliferation in response to carotid ligation injury. In an inducible plaque rupture model, Apoe-/-miR21-/- mice presented significantly higher atherothombotic events (93%, n=15) and signs of severe plaque instability compared to Apoe-/-miR21+/+ littermates (57%, n=14). In addition, Apoe-/-miR21-/- presented with an...