KEGG PATHWAY: map05417

PATHWAY: map05417

Entry

map05417                    Pathway

Name

Lipid and atherosclerosis

Description

Atherosclerosis is a chronic inflammatory disease marked by a narrowing of the arteries from lipid-rich plaques present within the walls of arterial blood vessels. It represents the root cause of the majority of cardiovascular diseases (CVDs) and their complications, including conditions such as coronary artery disease, myocardial infarction and stroke. An elevated level of low density lipoprotein (LDL) cholesterol constitutes a major risk factor for genesis of atherosclerosis. LDL can accumulate within the blood vessel wall and undergo modification by oxidation. Oxidized LDL (oxLDL) leads to endothelial dysfunction leading to expression of adhesion molecules and recruitment of monocyte in subendothelial space. The monocytes proliferate, differentiate into macrophages, and take up the lipoproteins, forming cholesterol-engorged "foam cells." With the time, the foam cells die, leaving a 'necrotic core' of crystalline cholesterol and cell debris. Smooth muscle cells proliferate and migrate into the region, laying down a protective cap over the lesion. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which mediates the recognition and internalization of oxLDL, is involved in all of these events critical in the pathogenesis of atherosclerosis.

Class

Human Diseases; Cardiovascular disease

Pathway map

map05417

Lipid and atherosclerosis

Disease

H02505

Atherosclerosis

Reference

PMID:23899566

Authors

Hopkins PN

Title

Molecular biology of atherosclerosis.

Journal

Physiol Rev 93:1317-542 (2013)
DOI:10.1152/physrev.00004.2012

Reference

PMID:22064431

Authors

Weber C, Noels H

Title

Atherosclerosis: current pathogenesis and therapeutic options.

Journal

Nat Med 17:1410-22 (2011)
DOI:10.1038/nm.2538

Reference

PMID:25869663

Authors

Tabas I, Garcia-Cardena G, Owens GK

Title

Recent insights into the cellular biology of atherosclerosis.

Journal

J Cell Biol 209:13-22 (2015)
DOI:10.1083/jcb.201412052

Reference

PMID:25614320

Authors

Tall AR, Yvan-Charvet L

Title

Cholesterol, inflammation and innate immunity.

Journal

Nat Rev Immunol 15:104-16 (2015)
DOI:10.1038/nri3793

Reference

PMID:31336709

Authors

Kattoor AJ, Goel A, Mehta JL

Title

LOX-1: Regulation, Signaling and Its Role in Atherosclerosis.

Journal

Antioxidants (Basel) 8:E218 (2019)
DOI:10.3390/antiox8070218

Reference

PMID:11985903

Authors

Mehta JL, Li D

Title

Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor.

Journal

J Am Coll Cardiol 39:1429-35 (2002)
DOI:10.1016/s0735-1097(02)01803-x

Reference

PMID:19286611

Authors

Li D, Mehta JL

Title

Intracellular signaling of LOX-1 in endothelial cell apoptosis.

Journal

Circ Res 104:566-8 (2009)
DOI:10.1161/CIRCRESAHA.109.194209

Reference

PMID:24886290

Authors

Lubrano V, Balzan S

Title

LOX-1 and ROS, inseparable factors in the process of endothelial damage.

Journal

Free Radic Res 48:841-8 (2014)
DOI:10.3109/10715762.2014.929122

Reference

PMID:23124189

Authors

Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P

Title

LOX-1 in atherosclerosis: biological functions and pharmacological modifiers.

Journal

Cell Mol Life Sci 70:2859-72 (2013)
DOI:10.1007/s00018-012-1194-z

Reference

PMID:21947818

Authors

Mitra S, Goyal T, Mehta JL

Title

Oxidized LDL, LOX-1 and atherosclerosis.

Journal

Cardiovasc Drugs Ther 25:419-29 (2011)
DOI:10.1007/s10557-011-6341-5

Reference

PMID:21338316

Authors

Lu J, Mitra S, Wang X, Khaidakov M, Mehta JL

Title

Oxidative stress and lectin-like ox-LDL-receptor LOX-1 in atherogenesis and tumorigenesis.

Journal

Antioxid Redox Signal 15:2301-33 (2011)
DOI:10.1089/ars.2010.3792

Reference

PMID:20203069

Authors

Ou HC, Song TY, Yeh YC, Huang CY, Yang SF, Chiu TH, Tsai KL, Chen KL, Wu YJ, Tsai CS, Chang LY, Kuo WW, Lee SD

Title

EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling.

Journal

J Appl Physiol (1985) 108:1745-56 (2010)
DOI:10.1152/japplphysiol.00879.2009

Reference

PMID:17614937

Authors

Chen XP, Zhang TT, Du GH

Title

Lectin-like oxidized low-density lipoprotein receptor-1, a new promising target for the therapy of atherosclerosis?

Journal

Cardiovasc Drug Rev 25:146-61 (2007)
DOI:10.1111/j.1527-3466.2007.00009.x

Reference

PMID:20181930

Authors

Mattaliano MD, Wooters J, Shih HH, Paulsen JE

Title

ROCK2 associates with lectin-like oxidized LDL receptor-1 and mediates oxidized LDL-induced IL-8 production.

Journal

Am J Physiol Cell Physiol 298:C1180-7 (2010)
DOI:10.1152/ajpcell.00483.2009

Reference

PMID:27073018

Authors

Salvador B, Arranz A, Francisco S, Cordoba L, Punzon C, Llamas MA, Fresno M

Title

Modulation of endothelial function by Toll like receptors.

Journal

Pharmacol Res 108:46-56 (2016)
DOI:10.1016/j.phrs.2016.03.038

Reference

PMID:23995626

Authors

Moore KJ, Sheedy FJ, Fisher EA

Title

Macrophages in atherosclerosis: a dynamic balance.

Journal

Nat Rev Immunol 13:709-21 (2013)
DOI:10.1038/nri3520

Reference

PMID:25403963

Authors

Butoi E, Gan AM, Manduteanu I

Title

Molecular and functional interactions among monocytes/macrophages and smooth muscle cells and their relevance for atherosclerosis.

Journal

Crit Rev Eukaryot Gene Expr 24:341-55 (2014)
DOI:10.1615/critreveukaryotgeneexpr.2014012157

Reference

PMID:24048132

Authors

Sheedy FJ, Moore KJ

Title

IL-1 signaling in atherosclerosis: sibling rivalry.

Journal

Nat Immunol 14:1030-2 (2013)
DOI:10.1038/ni.2711

Reference

PMID:21529710

Authors

Moore KJ, Tabas I

Title

Macrophages in the pathogenesis of atherosclerosis.

Journal

Cell 145:341-55 (2011)
DOI:10.1016/j.cell.2011.04.005

Reference

PMID:22577254

Authors

Gui T, Shimokado A, Sun Y, Akasaka T, Muragaki Y

Title

Diverse roles of macrophages in atherosclerosis: from inflammatory biology to biomarker discovery.

Journal

Mediators Inflamm 2012:693083 (2012)
DOI:10.1155/2012/693083

Reference

PMID:17442283

Authors

Collot-Teixeira S, Martin J, McDermott-Roe C, Poston R, McGregor JL

Title

CD36 and macrophages in atherosclerosis.

Journal

Cardiovasc Res 75:468-77 (2007)
DOI:10.1016/j.cardiores.2007.03.010

Reference

PMID:19065049

Authors

Park YM, Febbraio M, Silverstein RL

Title

CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima.

Journal

J Clin Invest 119:136-45 (2009)
DOI:10.1172/JCI35535

Reference

PMID:24903227

Authors

Park YM

Title

CD36, a scavenger receptor implicated in atherosclerosis.

Journal

Exp Mol Med 46:e99 (2014)
DOI:10.1038/emm.2014.38

Reference

PMID:21035758

Authors

Seimon TA, Nadolski MJ, Liao X, Magallon J, Nguyen M, Feric NT, Koschinsky ML, Harkewicz R, Witztum JL, Tsimikas S, Golenbock D, Moore KJ, Tabas I

Title

Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress.

Journal

Cell Metab 12:467-82 (2010)
DOI:10.1016/j.cmet.2010.09.010

Reference

PMID:25869517

Authors

Nimgulkar C, Ghosh S, Sankar AB, Uday KP, Surekha MV, Madhusudhanachary P, Annapurna BR, Raghu P, Bharatraj DK

Title

Combination of spices and herbal extract restores macrophage foam cell migration and abrogates the athero-inflammatory signalling cascade of atherogenesis.

Journal

Vascul Pharmacol 72:53-63 (2015)
DOI:10.1016/j.vph.2015.02.014

Reference

PMID:23928573

Authors

Canton J, Neculai D, Grinstein S

Title

Scavenger receptors in homeostasis and immunity.

Journal

Nat Rev Immunol 13:621-34 (2013)
DOI:10.1038/nri3515

Reference

PMID:20375591

Authors

Erridge C

Title

The roles of Toll-like receptors in atherosclerosis.

Journal

J Innate Immun 1:340-9 (2009)
DOI:10.1159/000191413

Reference

PMID:21884686

Authors

Seneviratne AN, Sivagurunathan B, Monaco C

Title

Toll-like receptors and macrophage activation in atherosclerosis.

Journal

Clin Chim Acta 413:3-14 (2012)
DOI:10.1016/j.cca.2011.08.021

Reference

PMID:21252151

Authors

Miller YI, Choi SH, Wiesner P, Fang L, Harkewicz R, Hartvigsen K, Boullier A, Gonen A, Diehl CJ, Que X, Montano E, Shaw PX, Tsimikas S, Binder CJ, Witztum JL

Title

Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity.

Journal

Circ Res 108:235-48 (2011)
DOI:10.1161/CIRCRESAHA.110.223875

Reference

PMID:20884885

Authors

Tabas I

Title

The role of endoplasmic reticulum stress in the progression of atherosclerosis.

Journal

Circ Res 107:839-50 (2010)
DOI:10.1161/CIRCRESAHA.110.224766