Targeting LOX-1 in atherosclerosis and vasculopathy: current knowledge and future perspectives

Ann N Y Acad Sci. 2019 May;1443(1):34-53. doi: 10.1111/nyas.13984. Epub 2018 Nov 1.

Abstract

LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1; also known as OLR1) is the dominant receptor that recognizes and internalizes oxidized low-density lipoproteins (ox-LDLs) in endothelial cells. Several genetic variants of LOX-1 are associated with the risk and severity of coronary artery disease. The LOX-1-ox-LDL interaction induces endothelial dysfunction, leukocyte adhesion, macrophage-derived foam cell formation, smooth muscle cell proliferation and migration, and platelet activation. LOX-1 activation eventually leads to the rupture of atherosclerotic plaques and acute cardiovascular events. In addition, LOX-1 can be cleaved to generate soluble LOX-1 (sLOX-1), which is a useful diagnostic and prognostic marker for atherosclerosis-related diseases in human patients. Of therapeutic relevance, several natural products and clinically used drugs have emerged as LOX-1 inhibitors that have antiatherosclerotic actions. We hereby provide an updated overview of role of LOX-1 in atherosclerosis and associated vascular diseases, with an aim to highlighting the potential of LOX-1 as a novel theranostic tool for cardiovascular disease prevention and treatment.

Keywords: LOX-1; OLR1; atherosclerosis; signaling pathway; therapeutic target; vascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Atherosclerosis / drug therapy*
  • Biomarkers / metabolism
  • Coronary Artery Disease / drug therapy*
  • Humans
  • Risk Factors
  • Scavenger Receptors, Class E / drug effects*
  • Scavenger Receptors, Class E / genetics
  • Scavenger Receptors, Class E / metabolism

Substances

  • Biomarkers
  • Scavenger Receptors, Class E