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IL‐10 polarizes macrophages in vivo to an anti‐inflammatory phenotype to improve cardiac remodeling post‐myocardial infarction
Author(s) -
Jung Mira,
Ma Yonggang,
Yabluchanskiy Andriy,
Iyer Rugmani Padmanabhan,
Lindsey Merry L
Publication year - 2016
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.30.1_supplement.1205.3
Subject(s) - medicine , myocardial infarction , ventricular remodeling , ventricle , macrophage polarization , m2 macrophage , cardiology , ligation , cardiac function curve , infiltration (hvac) , macrophage , heart failure , biology , in vitro , biochemistry , physics , thermodynamics
To evaluate the impact of aging on cardiac repair following myocardial infarction (MI), we enrolled 3–6 month old (young) and 18–23 month old (old) C57BL/6J mice. The mice were subjected to left coronary artery ligation and sacrificed at day 7 post‐MI. The survival rate was 38.9% for the young group and 77.8% for the old group. As excessive inflammatory response contributes to adverse remodeling of the left ventricle (LV) and mortality following MI, we evaluated inflammatory cell infiltration and macrophage polarization in the infarcted region. Histological analysis revealed the infiltration of macrophages in the old LV infarct was significantly lower than in young mice (p <0.05). We isolated macrophages from LV infarct region at day 7 post‐MI and assessed macrophage polarization by quantitative RT‐PCR. The M1 marker IL‐6 was significantly decreased and the M2 marker YM1 was significantly increased in the old mice (both p<0.05 vs. young). In the infarct LV, interleukin (IL)‐10 gene levels were higher in old than in young at day 7 post‐MI. To test whether IL‐10 explained the survival differences, young mice (n=21) were treated with IL‐10 (50 μg/kg/day) starting at day 1 post‐MI via osmotic mini‐pump and were sacrificed at day 7 post‐MI. IL‐10 treatment increased survival rate to 52.4%. IL‐10 treated mice showed improved LV function and decreased macrophage infiltration. Additionally, macrophages from IL‐10‐treated LV infarcts showed decreased M1 markers (CCL3, IFN‐γ, and TNF‐α) and increased M2 markers (Arg1 and Ym1). Our results indicate that in vivo IL‐10 polarizes macrophages to an anti‐inflammatory phenotype. Support or Funding Information This work was supported by the American Heart Association 14POST18770012, and 15SDG22930009, the National Institutes of Health 1R03EB009496, SC2HL101430, HHSN 268201000036C (N01‐HV‐00244), HL075360, P01HL051971, P20GM104357, and the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award 5I01BX000505