Abstract 16699: Chitinase-3-like-1 Reduces Reparative Inflammatory Cells and Exacerbates Cardiac Dysfunction After Myocardial Infarction
Introduction: Chitinase-3-like-1 (CHI3L1), a putative marker of inflammation and acute-phase reactant, is upregulated in human heart failure. Although elevated CHI3L1 serum levels correlate with cardiovascular morbidity, how it participates in heart failure remains untested.
Hypothesis: Supplementation of CHI3L1 following myocardial infarction (MI) would exacerbate heart failure through attenuating reparative inflammation.
Methods: Female C57BL/6J mice were subjected to MI for 2 or 35 d; CHI3L1 was measured by ELISA. To interrogate the effect of CHI3L1, mice were subjected to MI and treated with vehicle (PBS) or CHI3L1 (250 μg/kg, SQ) every other day immediately following surgical intervention until 35 d. Cardiac function was assessed via echocardiography 5 wk post MI. Isolectin B4 and Masson’s Trichrome were used to evaluate angiogenesis and fibrosis, respectively. The contribution of CHI3L1 supplementation to inflammation was assessed 7 d post MI by flow cytometry of inflammatory cells in the heart.
Results: CHI3L1 expression was upregulated in infarcted regions at 2 d (A) and 35 d (B) post MI. Treatment with CHI3L1 significantly diminished ejection fraction (C) and cardiac output (D). Ischemic zone capillary density was decreased 5 wk post MI (E). CHI3L1 treatment enhanced LV fibrosis (F). Total cardiac neutrophil deposition was decreased 7 d post MI in CHI3L1 treated hearts (data not shown). Recruitment of reparative N2 neutrophils (G) and Ly6C low macrophages (H) was significantly diminished with CHI3L1 treatment. No significant differences were observed among Ly6C high/low monocytes and lymphocyte populations.
Conclusions: CHI3L1 supplementation exacerbates cardiac dysfunction, suppresses capillary formation, and enhances cardiac fibrosis. CHI3L1 attenuates recruitment of pro-reparative inflammatory N2 neutrophils and LyC6 low macrophages. Thus, CHI3L1 represents a novel immunomodulatory target in the failing heart.
Author Disclosures: S. Dassanayaka: None. S. Muthusamy: None. Y. Kang: None. H. Li: None. S.P. Jones: None. M. Wysoczynski: None.
- © 2016 by American Heart Association, Inc.