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LOX-1 in atherosclerosis: biological functions and pharmacological modifiers

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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.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81072641); NSFC-CIHR CHINA-CANADA Joint Health Research Initiative Proposal (No. 30811120434); National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” (No. 2009ZX09102-152, 2011ZX09401-307); Team Item of Natural Science Foundation of Guangdong Province (No. S2011030003190); Major Project of Guangdong Province (No. 2008A030201013, No. 2012A080201007); Major Project of Department of Education of Guangdong Province (No. CXZD1006). General work in this area has also been supported by grants from the National Health and Medical Research Council of Australia, National Heart Foundation of Australia and Diabetes Australia Research Trust. Suowen Xu received the “New Investigator Award” from Ministry of Education of China. We gratefully acknowledge the contributions of investigators dedicated to the LOX-1 field, and apologize to those investigators whose work we could not cite owing to space limitations.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Suowen Xu & Joel Moss

  2. Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China

    Suowen Xu & Peiqing Liu

  3. Faculty of Medicine, Surugadai-Hospital of Nihon University, Chiyoda-ku, Tokyo, 101-8309, Japan

    Sayoko Ogura

  4. Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Jiawei Chen

  5. Discipline of Pharmacy, School of Medical Sciences and Diabetes Complications Group, Health Innovations Research Institute, RMIT University, Melbourne, VIC, 3083, Australia

    Peter J. Little

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  1. Suowen Xu
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  2. Sayoko Ogura
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  3. Jiawei Chen
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Correspondence to Suowen Xu or Peiqing Liu.

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Xu, S., Ogura, S., Chen, J. et al. LOX-1 in atherosclerosis: biological functions and pharmacological modifiers. Cell. Mol. Life Sci. 70, 2859–2872 (2013). https://doi.org/10.1007/s00018-012-1194-z

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  • DOI: https://doi.org/10.1007/s00018-012-1194-z

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