Abstract 14105: Apoptosis Inhibitor of Macrophage Activates Inflammatory Response After Acute Myocardial Infarction
Introduction: The persistent inflammation response after myocardial infarction increases myocardial injury, and causes heart failure due to cardiac dysfunction and remodeling. TLR-4 was activated by the recognition of not only pathogen-associated molecular patterns but also endogenous ligands and it serves as a proinflammatory function in circumstances involving myocardial tissue injury. Whereas, it was reported the apoptosis inhibitor of macrophage (AIM) provoke an efflux of saturated free fatty acid, one of the TLR-4 ligands, due to lipolysis, which causes the chronic inflammation via TLR-4 pathway in adipose tissue.
Hypothesis: This study investigated the hypothesis that AIM activates a proinflammatory response after myocardial infarction.
Methods: The ligation of the left anterior descending coronary artery to induced myocardial infarction was performed on both AIM-deficient (AIM-/-) mice and wild-type mice. After 3 days, the inflammation responses were assessed in TLR-4/NFkB activation pathway. And infarct size/area-at-risk was measured by staining with Evans blue and triphenyltetrazolium chloride. In addition, the left ventricular remodeling was examined after 28 days.
Results: AIM-/- mice showed significantly smaller infarct size compared with wild-type mice given similar area at risk (20.8±0.6% vs. 27.8±1.9%, p=0.02). In AIM-/- mice with reduction of plasma free fatty acid, IRAK4 in TLR-4/NFkB pathway and NFkB activity were decreased on myocardium (p=0.02, 0.03 vs. wild-type, respectively). Moreover, there was the reduction of myeloperoxidase activity and iNOS in the inflammation response (p<0.01, p=0.03, respectively). We found that the NFkB DNA-binding activation via TLR-4, neutrophil infiltration, and inflammatory mediator were decreased in AIM-/- mice compared with wild-type mice after 3days. And, the heart weight to body weight ratio, myocardial fibrosis of AIM-/- mice were decreased, and a survival rate improved after 28 days (p<0.01).
Conclusions: AIM-/- mice demonstrated less inflammation response and smaller infarction size after myocardial infarction, suggesting AIM may activate a proinflammatory of TLR-4 after myocardial infarction.
- Apoptosis inhibitor of macrophage
- Toll-like receptors-4
- myocardial infarction
- free fatty acid
Author Disclosures: T. Nishikido: None. A. Shiraki: None. J. Oyama: Research Grant; Modest; Fukuda Denshi Co, Ltd. K. Node: Research Grant; Significant; Astellas Pharma Inc, Nippon Boehringer Ingelheim Co, Ltd, Daiichi Sankyo Company, Ltd, Takeda Pharmaceutical Co, Ltd, Mitsubishi Tanabe Pharma Corporation, and MSD K.K.. Other Research Support; Modest; Astellas Pharma Inc, Nippon Boehringer Ingelheim Co, Ltd, Daiichi Sankyo Company, Ltd, Takeda Pharmaceutical Co, Ltd, Mitsubishi Tanabe Pharma Corporation, and MSD K.K.. Speakers Bureau; Significant; AstraZeneca, Astellas Pharma Inc, Nippon Boehringer Ingelheim Co, Ltd, Pfizer Inc, MSD K.K., Daiichi Sankyo Company, Ltd, Kowa Pharmaceutical Co, Ltd, Takeda Pharmaceutical Co, Ltd, Novartis Pharmace.
- © 2015 by American Heart Association, Inc.