The role of LOX-1, a novel lectin-like receptor for oxidized low density lipoprotein, in atherosclerosis.
There is strong evidence for the role of oxidative stress in all stages of atherosclerosis. Oxidized low density lipoprotein (ox-LDL), a marker of oxidative stress, is present in the plasma as well as in the atherosclerotic arteries of patients with atherosclerosis. Ox-LDL leads to endothelial activation, dysfunction and injury. Recently, a novel lectin-like receptor for ox-LDL (LOX-1) has been identified, primarily in the endothelial cells, that allows uptake of ox-LDL into endothelial cells. This receptor is transcriptionally upregulated by tumour necrosis factor-a, angiotensin II, shear stress and ox-LDL. The expression of this receptor activates a variety of intracellular processes that leads to expression of adhesion molecules and endothelial activation. Recent studies show that LOX-1 activation leads to the expression of CD40/40 L in endothelial cells and upregulation of matrix metalloproteinases. This receptor is highly expressed in blood vessels of animals and humans with hypertension, diabetes mellitus and atherosclerosis. Co-localization of LOX-1 along with ox-LDL in the rupture-prone plaque suggests that this receptor may be involved in the precipitation of acute myocardial ischemia. Identification and regulation of this receptor and understanding of signal transduction pathways may lead to new therapies in disease states characterized by endothelial dysfunction.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA
Jawahar L
JL
Mehta
D000804:Angiotensin II / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology*; D003920:Diabetes Mellitus / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D011237:Predictive Value of Tests; D051131:Receptors, Oxidized LDL / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015398:Signal Transduction
D015415:Biomarkers; D008077:Lipoproteins, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D000804:Angiotensin II