Abstract 10946: Blockade of NKG2D / NKG2D Ligands Interaction Attenuated Cardiac Remodeling After Myocardial Infarction
The activating receptor Natural Killer Group 2 member D (NKG2D), expressed on immune cells such as NK, NKT and γδ T cells, contributes to eliminating infected or tumor cells by recognizing NKG2D ligands (NKG2DL). Accumulating evidence demonstrates that immune responses are involved in cardiovascular diseases; however, how cardiomyocyte death is induced by immune reactions in heart failure remains to be fully elucidated. Here, we examined the involvement of NKG2D/NKG2DL-mediated cell death in the progression of heart failure after myocardial infarction (MI).
Methods and Results
Murine MI was generated by ligating left anterior descending artery. Quantitative reverse transcription polymerase chain reaction (RT-PCR) demonstrated that NKG2DL, especially Rae-1ε, and NKG2D were up-regulated and reached the peak at day 3 (32 fold v.s. control) and day 7 (22 fold v.s. control), respectively, after MI. Moreover, immunohistochemical analysis revealed that Rae-1 was expressed in the infarct and border area of the post-infarcted hearts. To identify the NKG2D-expressing cells which infiltrated post-infarcted myocardium, flow cytometric analysis was performed using anti-CD49b antibody, NK cell marker, or anti-γδ TCR antibody, γδ T cell marker. Intriguingly, NKG2D-expressing immune cells were mainly γδ T cells, but not NK cells. Finally, to examine the pathophysiological role of the NKG2D/NKG2DL interaction in cardiac remodeling, MI mice were intraperitoneally treated with anti-Rae-1ε antibody or control IgG. Anti-Rae-1ε antibody administration suppressed cardiac fibrosis at day 14 after MI compared with control (control: 45.5%, anti-Rae-1ε antibody: 30.2%) assessed by Masson’s trichrome staining. Furthermore, TUNEL staining showed that apoptosis of cardiomyocytes was reduced by anti-Rae-1ε antibody treatment at day 3 after MI.
Blockade of NKG2D/NKG2DL interaction suppressed cardiac injury and death, preventing the progression of heart failure. NKG2D/NKG2DL could be a novel therapeutic target for heart failure.
Author Disclosures: K. Matsumoto: None. M. Obana: None. R. Hashizume: None. Y. Yokoyama: None. S. Miyagawa: None. T. Mohri: None. M. Maeda: None. H. Nakayama: None. Y. Sawa: None. Y. Fujio: Research Grant; Modest; DAIICHI SANKYO COMPANY, LIMITED, Takeda Pharmaceutical Company Limited, Pfizer Inc.. Research Grant; Significant; Bristol-Myers Squibb Company.
- © 2015 by American Heart Association, Inc.