MCP-1/CCL2 as a therapeutic target in myocardial infarction and ischemic cardiomyopathy.
The CC chemokine Monocyte Chemoattractant Protein (MCP)-1/CCL2 mediates recruitment of mononuclear cells, modulates monocyte and lymphocyte phenotype and regulates fibrous tissue deposition and angiogenesis. MCP-1 is markedly induced in the infarcted myocardium and plays an important role in infarct healing and post-infarction remodeling. MCP-1 null mice exhibit decreased macrophage recruitment in the infarcted heart, delayed phagocytosis of dead cardiomyocytes, diminished fibroblast infiltration and attenuated left ventricular remodeling. Targeted deletion of CCR2, the primary MCP-1 receptor also protects from the development of adverse remodeling following myocardial infarction. In addition to its role in infarct healing, MCP-1 signaling plays an important role in the development of interstitial fibrosis in a mouse model of brief repetitive myocardial ischemia and reperfusion. Our review manuscript discusses the mechanisms responsible for MCP-1-mediated effects in the ischemic myocardium and explores MCP-1 targeting as a novel therapeutic approach in patients with myocardial infarction and ischemic non-infarctive cardiomyopathy.
Xia
Ying
Y
Section of Cardiovascular Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Frangogiannis
Nikolaos G
NG
D000818:Animals; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000150:complications; D015398:Signal Transduction / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D018932:Chemokine CCL2