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Endogenous CXCL10/Interferon‐γ‐Inducible Protein (IP)‐10 orchestrates myocardial infarct healing
Author(s) -
Bujak Marcin J.,
Leucker Thorsten,
Zymek Pawel,
Veeranna Vikas,
Huebener Peter,
Tager Andrew,
Luster Andrew,
Frangogiannis Nikolaos
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.466.10
Subject(s) - fibrosis , angiogenesis , medicine , myocardial infarction , m2 macrophage , cardiac fibrosis , ventricle , myofibroblast , inflammation , cxcl10 , chemokine , macrophage , chemistry , in vitro , biochemistry
IP‐10, a chemoattractant for effector T cells with angiostatic and anti‐fibrotic properties, is markedly but transiently induced in the infarcted heart. We hypothesized that endogenous IP‐10 may suppress premature angiogenesis and fibrosis in the infarct until the wound is debrided and the local environment can support fibrous tissue deposition. Histomorphometric, molecular and echocardiographic endpoints were compared between IP‐10 −/− and WT mice undergoing reperfused infarction protocols. IP‐10 −/− mice exhibited increased neutrophil and macrophage density in the infarcted area. mRNA expression of the CC chemokine MCP‐1 was significantly higher in IP‐10 −/− infarcts; however, cardiac mRNA levels of the pro‐inflammatory cytokines IL‐1β, TNF‐α and IL‐6 were comparable with WT animals. Myofibroblast density was increased in infarcted IP‐10 −/− hearts resulting in increased collagen deposition in the infarct and the peri‐infarct area. Enhanced inflammation and fibrosis in IP‐10 −/− mice was associated with extension of the scar, worse systolic dysfunction and increased dilation of the infarcted ventricle. IP‐10 deficiency results in disturbed orchestration of post‐infarction cardiac repair, enhanced fibrosis and accentuated adverse remodeling (R01 HL‐76246).