Affiliation:
1. Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States
Abstract
Oxidized LDL (ox-LDL) plays a central role in atherosclerosis by acting on multiple
cells such as endothelial cells, macrophages, platelets, fibroblasts and smooth muscle cells
through LOX-1. LOX-1 is a 50 kDa transmembrane glycoprotein that serves as receptor for
ox-LDL, modified lipoproteins, activated platelets and advance glycation end-products. Ox-
LDL through LOX-1, in endothelial cells, causes increase in leukocyte adhesion molecules,
activates pathways of apoptosis, increases reactive oxygen species and cause endothelial dysfunction.
In vascular smooth muscle cells and fibroblasts, they stimulate proliferation, migration
and collagen synthesis. LOX-1 expressed on macrophages inhibit macrophage migration
and stimulate foam cell formation. They also stimulate generation of metalloproteinases and
contribute to plaque instability and thrombosis. Drugs that modulate LOX-1 are desirable targets
against atherosclerosis. Many naturally occurring compounds have been shown to modulate
LOX-1 expression and atherosclerosis. Currently, novel drug design techniques are used
to identify molecules that can bind to LOX-1 and inhibit its activation by ox-LDL. In addition,
techniques using RNA interference and monoclonal antibody against LOX-1 are currently
being investigated for clinical use.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
Cited by
212 articles.
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