Chemokines in myocardial ischemia.
Chemokine expression is markedly upregulated in healing myocardial infarcts and may play an important role in regulating leukocyte infiltration and activity and in modulating infarct angiogenesis as well as fibrous tissue deposition. The CC chemokine monocyte chemoattractant protein-1/CCL2 has important effects in infarct healing. Monocyte chemoattractant protein-1 -/- mice exhibit reduced macrophage infiltration and activation, suppressed cytokine synthesis, delayed phagocytotic removal of dead cardiomyocytes, diminished myofibroblast accumulation, and decreased ventricular remodeling after myocardial infarction. Monocyte chemoattractant protein-1 may also play an important role in the development of interstitial fibrosis in ischemic noninfarctive cardiomyopathy. CXC chemokines are also induced in healing infarcts. Interleukin-8/CXCL8 may mediate neutrophil recruitment and activation and may promote neovessel formation, whereas induction of the angiostatic and antifibrotic chemokine interferon-gamma-inducible protein-10/CXCL10 may serve to prevent premature wound angiogenesis and fibrous tissue deposition in the infarct, until the injured myocardium has been cleared from dead cells and debris and a fibrin-rich provisional matrix is formed. Understanding of the role of chemokines in myocardial ischemia may result in novel strategies in the treatment of patients with ischemic heart disease.
Frangogiannis
Nikolaos G
NG
Section of Cardiovascular Sciences, The Methodist Hospital and the DeBakey Heart Center, Baylor College of Medicine, One Baylor Plaza M/S F-602, Houston, TX 77030, USA. ngf@bcm.tmc.edu
Entman
Mark L
ML
D000818:Animals; D018925:Chemokines / Q000145:classification / Q000378:metabolism*; D006801:Humans; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
D018925:Chemokines