LOX-1 in atherosclerosis: biological functions and pharmacological modifiers
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Cellular and Molecular Life Sciences
REVIEW
LOX-1 in atherosclerosis: biological functions and pharmacological modifiers Suowen Xu • Sayoko Ogura • Jiawei Chen Peter J. Little • Joel Moss • Peiqing Liu
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Received: 7 August 2012 / Revised: 4 October 2012 / Accepted: 8 October 2012 Ó Springer Basel 2012
Abstract Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1, also known as OLR-1), is a class E scavenger receptor that mediates the uptake of oxLDL by vascular cells. LOX-1 is involved in endothelial dysfunction, monocyte adhesion, the proliferation, migration, and apoptosis of smooth muscle cells, foam cell formation, platelet activation, as well as plaque instability; all of these events are critical in the pathogenesis of atherosclerosis. These LOX-1-dependent biological processes contribute to plaque instability and the ultimate clinical sequelae of plaque rupture and life-threatening tissue ischemia. Administration of anti-LOX-1 antibodies inhibits atherosclerosis by decreasing these cellular events. Over the past decade, multiple drugs including naturally occurring
antioxidants, statins, antiinflammatory agents, antihypertensive and antihyperglycemic drugs have been demonstrated to inhibit vascular LOX-1 expression and activity. Therefore, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases. This review aims to integrate the current understanding of LOX-1 signaling, regulation of LOX-1 by vasculoprotective drugs, and the importance of LOX-1 in the pathogenesis of atherosclerosis. Keywords Atherosclerosis Oxidized LDL LOX-1 Soluble LOX-1 Review
Introduction S. Xu (&) J. Moss Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA e-mail: [email protected] S. Xu P. Liu (&) Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China e-mail: [email protected] S. Ogura Faculty of Medicine, Surugadai-Hospital of Nihon University, Chiyoda-ku, Tokyo, 101-8309, Japan J. Chen Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China P. J. Little Discipline of Pharmacy, School of Medical Sciences and Diabetes Complications Group, Health Innovations Research Institute, RMIT University, Melbourne, VIC 3083, Australia
Atherosclerosis-related cardiovascular diseases continue to be a major cause of morbidity and mortality in developed and developing countries. Atherosclerosis is a multifactorial disease for which many mechanisms are known, but the cellular and molecular mechanisms precipitating the disease process are not well defined. Atherosclerosis commences with the binding and retention of lipids by modified proteoglycans with hyperelongated glycosaminoglycan chains, followed by a multifactorial inflammatory process [1–4]. Cellular and cytokine-based inflammatory processes represent novel therapeutic targets for the prevention and treatment of atherosclerosis [5]. After
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