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Macrophage Depletion Suppresses Sympathetic Hyperinnervation following Myocardial Infarction
Author(s) -
Wernli Gwenaelle,
Hasan Wohaib,
Smith Peter G.
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.1234.8
Subject(s) - medicine , myocardial infarction , myofibroblast , sympathetic nervous system , saline , endocrinology , macrophage , inflammation , neurotrophin , cardiology , receptor , biology , fibrosis , biochemistry , in vitro , blood pressure
Myocardial infarction is followed by sympathetic axon sprouting in the peri‐infarct region and this has been associated with arrhythmias leading to sudden cardiac death. Inflammatory cells expressing nerve growth factor, a potent sympathetic neurotrophic protein, are frequent residents of the infarct, leading to the hypothesis that these cells may contribute to sympathetic sprouting. Our goal was to determine if macrophages are obligatory for sympathetic hyperinnervation. Ovariectomized female rats received left coronary artery ligation (CAL) or sham operation, followed by injections of saline vehicle or clodronate liposomes to kill macrophages. Sham‐operated myocardium contained sympathetic axons (0.9 ± 0.06% of section area), few myofibroblasts and no macrophages or T‐cells. In the saline‐injected CAL group, sympathetic innervation was increased two‐fold and the peri‐infarct contained myofibroblasts (134,374 ± 9,710 μm 2 /mm 2 section), macrophages (1,195 ± 97/mm 2 ) and T‐cells (412 ± 27/mm 2 ). Treatment for 7 days with clodronate liposomes reduced sympathetic innervation to control levels. Macrophages were reduced by 69% and myofibroblasts area was reduced by 23%, but the number of T‐cells was comparable to untreated CAL rats. These results indicate that macrophages are required for the development of sympathetic hyperinnervation following myocardial infarction. Supported by HL079652