Title

Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications

Authors

Authors

J. L. Niu;P. E. Kolattukudy

Comments

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Abbreviated Journal Title

Clin. Sci.

Keywords

angiogenesis; atherosclerosis; inflammation; ischaemic cardiomyopathy; monocyte chemotactic protein-1 (MCP-1); MONOCYTE CHEMOATTRACTANT PROTEIN-1; TYPE-2 DIABETES-MELLITUS; CHEMOKINE; RECEPTOR CCR2; EXPERIMENTAL AUTOIMMUNE MYOCARDITIS; INDUCED; INSULIN-RESISTANCE; ACUTE CORONARY SYNDROMES; ISCHEMIC-HEART-DISEASE; TRANSCRIPTION FACTOR; ALLOGRAFT-REJECTION; GENE-EXPRESSION; Medicine, Research & Experimental

Abstract

Many of the major diseases, including cardiovascular disease, are widely recognized as inflammatory diseases. MCP-1 (monocyte chemotactic protein-1) plays a critical role in the development of cardiovascular diseases. MCP-1, by its chemotactic activity, causes diapedesis of monocytes from the lumen to the subendothelial space where they become foam cells, initiating fatty streak formation that leads to atherosclerotic plaque formation. Inflammatory macrophages probably play a role in plaque rupture and the resulting ischaemic episode as well as restenosis after angioplasty. There is strong evidence that MCP-1 plays a major role in myocarditis, ischaemia/reperfusion injury in the heart and in transplant rejection. MCP-1 also plays a role in cardiac repair and manifests protective effects under certain conditions. Such protective effects may be due to the induction of protective ER (endoplasmic reticulum) stress chaperones by MCP-1. Under sustained ER stress caused by chronic exposure to MCP-1, the protection would break down resulting in the development of heart failure. MCP-1 is also involved in ischaemic angiogenesis. The recent advances in our understanding of the molecular mechanisms that might be involved in the roles that MCP-1 plays in cardiovascular disease are reviewed. The gene expression changes induced by the signalling events triggered by MCP-1 binding to its receptor include the induction of a novel zinc-finger protein called MCP-1 (MCP-1-1nduced protein), which plays critical roles in the development of the pathophysiology caused by MCP-1 production. The role of the MCP-1/CCR2 (CC chemokine receptor 2) system in diabetes, which is a major risk factor for cardiovascular diseases, is also reviewed briefly. MCP-1/CCR2-and/or MCPIP-targeted therapeutic approaches to intervene in inflammatory diseases, including cardiovascular diseases, may be feasible.

Journal Title

Clinical Science

Volume

117

Issue/Number

3-4

Publication Date

1-1-2009

Document Type

Review

Language

English

First Page

95

Last Page

109

WOS Identifier

WOS:000268647500001

ISSN

0143-5221

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