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Role of Ox-LDL and LOX-1 in Atherogenesis

[ Vol. 26 , Issue. 9 ]

Author(s):

Ajoe John Kattoor, Sri Harsha Kanuri and Jawahar L. Mehta*   Pages 1693 - 1700 ( 8 )

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.

Keywords:

Ox-LDL and LOX-1, LOX-1 atherosclerosis, Endothelial cells LOX-1, oxidative stress LOX-1, Oxidized LDL, atherogenesis, oxidized LDL.

Affiliation:

Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205



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