LOX-1: A Critical Player in the Genesis and Progression of Myocardial Ischemia

Myocardial ischemia is the most common cause of mortality and morbidity in the developed countries and rapidly becoming a common malady in the developing countries. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the OLR1 gene, is a scavenger receptor that plays a fundamental role in the genesis and progression of atherosclerosis and its complications. LOX-1 has been identified as a major receptor for oxidized low-density lipoprotein (ox-LDL) in endothelial cells, cardiomyocytes and fibroblast. In vitro and in vivo studies show that LOX-1 is upregulated during acute myocardial ischemia, and continues to be upregulated during chronic ischemia. Further, LOX-1 inhibition reduces ischemic myocardial injury and limits cardiac remodeling. LOX-1 inhibition decreases oxidative stress and inflammatory response to injury resulting in limitation of ischemic injury. Molecular studies show that LOX-1 inhibition reduces release of pro-inflammatory cytokines and expression of angiotensin II type 1 receptor via inhibition of redox-sensitive pathways. These alterations limit cardiomyocyte hypertrophy and collagen accumulation in the ischemic regions. These alterations in molecular signaling and physical alterations can result in improved cardiac function and better survival after ischemic myocardial injury.