Abstract 12680: Silencing miR-145 Prevents Potentiating Effects of Human Electronegative Low-Density Lipoprotein on Platelet Activation

Background: During ST-elevation myocardial infarction (STEMI) and ischemic stroke, platelet activation triggers thrombosis. Low-density lipoprotein in human plasma can be chromatographically resolved into 5 subfractions (L1-L5); L5, the most electronegative and atherogenic subfraction, is significantly elevated in patients with these acute ischemic events. Whereas L5 potentiates platelet activation and aggregation by activating nuclear factor kappa B (NF-κB), L1 does not. Because NF-κB can be negatively regulated by ubiquitin-specific peptidase 31 (USP31), we examined whether L5-mediated thrombosis can be prevented by silencing microRNA (miR)-145, an upstream modulator of USP31. Methods and Results: Cultivated human platelets were treated with L5 or L1 from STEMI or stroke patients. L5, but not L1, induced phosphorylation of IκB kinase β (IKKβ) and degradation of its inhibitor IκBα, thereby activating NF-κB. These effects were prevented by neutralizing LOX-1, the lectin-like receptor that mediates L5 sign...