Document Detail


Chemokines in the ischemic myocardium: from inflammation to fibrosis.
MedLine Citation:
PMID:  15693606     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Myocardial infarction is associated with an inflammatory response leading to leukocyte recruitment, healing and formation of a scar. Members of the chemokine superfamily are rapidly induced in the infarcted myocardium and may critically regulate the post-infarction inflammatory response. CXCL8/Interleukin (IL)-8 is upregulated in the infarcted area and may induce neutrophil infiltration. In addition, mononuclear cell chemoattractants, such as the CC chemokines CCL2/Monocyte Chemoattractant Protein (MCP)-1, CCL3/Macrophage Inflammatory Protein (MIP)1alpha, and CCL4/MIP-1beta are expressed in the ischemic area, and may regulate monocyte and lymphocyte recruitment. However, chemokines may have additional effects on healing infarcts beyond their leukotactic properties. The CXC chemokine CXCL10/Interferon-y inducible Protein (IP)-10, a potent angiostatic factor with antifibrotic properties, is induced in the infarct and may prevent premature angiogenesis and fibrous tissue deposition, until the infarct is debrided and provisional matrix necessary to support granulation tissue ingrowth is formed. Chemokine induction in the infarct is transient, suggesting that inhibitory mediators (such as transforming growth Factor (TGF)-beta) may be activated suppressing chemokine synthesis and leading to resolution of inflammation and transition to fibrosis. Brief repetitive ischemia in mice also results in chemokine upregulation followed by suppression of chemokine synthesis and interstitial fibrosis, in the absence of myocardial infarction. Chemokine expression may play a role in the pathogenesis of non-infarctive ischemic cardiomyopathy, where early ischemia-induced chemokine expression may be followed by activation of inhibitory mediators that suppress inflammation, but induce fibrosis.
Authors:
N G Frangogiannis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Inflammation research : official journal of the European Histamine Research Society ... [et al.]     Volume:  53     ISSN:  1023-3830     ISO Abbreviation:  Inflamm. Res.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2005-02-07     Completed Date:  2005-11-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9508160     Medline TA:  Inflamm Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  585-95     Citation Subset:  IM    
Affiliation:
Section of Cardiovascular Sciences, The Methodist Hospital and the DeBakey Heart Center, One Baylor Plaza M/S F-602, Houston TX 77030, USA. ngf@bcm.tmc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Chemokine CCL2 / antagonists & inhibitors,  biosynthesis
Chemokines / biosynthesis*,  immunology
Fibrosis
Humans
Interleukin-8 / biosynthesis
Myocardial Infarction / immunology*,  pathology
Myocardial Reperfusion
Myocarditis / etiology,  immunology*,  pathology
Receptors, Cytokine / biosynthesis
Ventricular Remodeling
Grant Support
ID/Acronym/Agency:
HL-42550/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CCL2; 0/Chemokines; 0/IP10-Mig receptor; 0/Interleukin-8; 0/Receptors, Cytokine

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