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Oxidized LDL, LOX-1 and Atherosclerosis

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Abstract

An elevated level of low density lipoprotein (LDL) cholesterol constitutes a major risk factor for genesis of atherosclerosis. Ox-LDL plays a more important role in the genesis and progression of atherosclerosis than the native LDL. Ox-LDL leads to endothelial dysfunction leading to expression of adhesion molecules and recruitment of monocyte in subendothelial space. Ox-LDL is taken up by macrophages via scavenger receptors, such as SR-A1, SR-A2 and LOX-1. Lately, LOX-1, a type II membrane protein receptor of ox-LDL, has gained much importance in relation to effects of ox-LDL on endothelial biology. Endothelial cells primarily express LOX-1 as receptor for ox-LDL and ox-LDL has been shown to upregulate expression of LOX-1. In addition, ox-LDL promotes the growth and migration of smooth muscle cells, monocytes/macrophages and fibroblasts. In this review we discuss the role of ox-LDL and LOX-1 in genesis and progression of atherosclerosis.

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Abbreviations

Ox-LDL:

Oxidized low density lipoprotein

LOX-1:

Lectin-like low density lipoprotein receptor

NO:

Nitric oxide

eNOS:

Endothelial nitric oxide synthetase

SOD:

Superoxide dismutase

ET-1:

Endothelin-1

RAGE:

Receptor for advanced glycation end products

BH4:

Tetrahydrobiopterin

SR-A1:

Scavenger receptor A1

SR-A2:

Scavenger receptor A2

AGE:

Advanced glycation end product

AT1R:

Angiotensin II Type 1 Receptor

Ang II:

Angiotensin II

NADPH:

Nicotinamide adenine dinucleotide phosphate dehydogenase

MAPK:

Mitogen activated protein kinases

NFκB:

Nuclear factor kappa beta

ETB:

Endothelin receptor B

HUVEC:

Human umbilical vein endothelial cells

LOX-1 KO mice:

Lectin-like oxidized low density lipoprotein knockout mice

LDLR KO mice:

Low density lipoprotein receptor knockout mice

MMP:

Matrix metalloproteinase

AP1:

Activating protein −1

dil:

1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate

NOX-4:

NADPH oxidase-4

TGF-β1:

Transforming growth factor beta 1

APO E KO mice:

Apolipoprotein E knockout mice

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Correspondence to Sona Mitra.

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Mitra, S., Goyal, T. & Mehta, J.L. Oxidized LDL, LOX-1 and Atherosclerosis. Cardiovasc Drugs Ther 25, 419–429 (2011). https://doi.org/10.1007/s10557-011-6341-5

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