Abstract 18189: Direct Binding of LOX-1 With AT1 Receptors Mediates Ox-LDL-Induced Cardiomyocyte Hypertrophy

Introduction: Lectin-like oxidized low-density lipoprotein (ox-LDL) and its receptor LOX-1 as well as angiotensin II (AngII) and its type 1 receptor (AT1-R) have been implicated in the development of cardiomyocye hypertrophy, however, the relationship between them remains unknown. Hypothesis: We here demonstrate that ox-LDL induces hypertrophic responses by stimulating direct association and interaction of LOX-1 with AT1-R. Methods: Ox-LDL (250 ng/kg/min), AngII (200 ng/kg/min),Losartan (3 mg/kg/day), LOX-1 neutralizing antibody (0.6 mg/kg/day) and Enalapril (10 mg/kg/day) were continuously administered by Alzet osmotic minipumps implanted subcutaneously into the mice. Transthoratic echocardiography was performed. Results: Ox-LDL induced hypertrophic responses both in vivo and in vitro, which could be abolished following inhibition of either LOX-1 or AT1-R by both pharmacologic and RNA silence methods but not by attenuation of AngII, suggesting that LOX-1 and AT1-R rather than AngII are critically involve...