Developing successful immunomodulatory therapies against ventricular remodeling after myocardial infarction

开发成功的针对心肌梗死后心室重塑的免疫调节疗法

• 批准号: 23390217
• 负责人: SANO MOTOAKI
• 金额: $ 12.31万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390217/
• 关键词: 心筋梗塞; 心不全; 免疫; 肺水腫; NK細胞; 好中球; IL-10; 線維化; 樹状細胞; リンパ球; マクロファージ

Left ventricular (LV) remodeling leads to chronic heart failure and is a main determinant of morbidity and mortality after myocardial infarction (MI). Mice with DC ablation showed deteriorated LV function and remodeling concomitant with enhanced expression of IL-1beta, IL-18, and TNF-alpha, prolonged extracellular matrix degradation, marked infiltration of proinflammatory monocytes. A deficiency of gamma-delta T cells improved survival, limiting infarct expansion and fibrosis in noninfarcted myocardium and alleviating LV dilatation and systolic dysfunction after MI. IL-17A-producing gamma-delta T cells promotes sustained infiltration of neutrophils and macrophages, , aggravating cardiomyocyte death, and enhancing fibroblast proliferation. Depletion of NK cells from mice exhibited severe respiratory. Adoptive transfer of NK cells from wild-type mice, but not from IL-10 knockout mice, into the NK cell-depleted mice rescued the respiratory phenotype.

左心室（LV）重构导致慢性心力衰竭，是心肌梗死（MI）后发病率和死亡率的主要决定因素。DC消融小鼠显示左室功能恶化和重构，伴随IL-1 β、IL-18和TNF-α表达增强，细胞外基质降解延长，促炎性单核细胞显著浸润。缺乏γ-δ T细胞可改善存活率，限制非梗死心肌的梗死扩展和纤维化，减轻MI后的LV扩张和收缩功能障碍。产生IL-17 A的γ-δ T细胞促进嗜中性粒细胞和巨噬细胞的持续浸润，加重心肌细胞死亡，并增强成纤维细胞增殖。来自小鼠的NK细胞的消耗表现出严重的呼吸道感染。将来自野生型小鼠而非IL-10敲除小鼠的NK细胞连续转移到NK细胞耗尽的小鼠中拯救了呼吸表型。

项目成果

IL-17 Produced from γ δ T cells Promote Left Ventricular Remodeling after Myocardial Infarction

γδT细胞产生的IL-17促进心肌梗死后左心室重塑

• 发表时间: 2012
• 作者: Xiaoxiang Yan;Motoaki Sano;Takashi Shichita;Tomohiro Matsuhashi;Yoshinori Katsumata;Akihiko Yoshimura;Keiichi Fukuda
• 通讯作者: Keiichi Fukuda

IL-17 Produced from γδT Cells Promote Left Ventricular Remodeling after Myocardial Infarction

γδT 细胞产生的 IL-17 促进心肌梗死后左心室重塑

• 发表时间: 2012
• 作者: Ashihara T;Haraguchi R;Nakazawa K;Namba T;Ikeda T;Nakazawa Y;Ozawa T;Ito M;Horie M;Trayanova NA;藪本千鶴;〓小響
• 通讯作者: 〓小響

Diverse stage-dependent effects of glucocorticoids in a murine model of viral myocarditis.

• DOI: 10.1016/j.jjcc.2012.11.006
• 发表时间: 2013-03
• 期刊: Journal of cardiology
• 影响因子: 2.5
• 作者: Hiroshi Nakamura;I. Kunitsugu;K. Fukuda;M. Matsuzaki;M. Sano

Deleterious Effect of IL-23/IL-17 Axis and γ δ T Cells in Left Ventricular Remodeling after Myocardial Infarction

IL-23/IL-17轴和γδT细胞对心肌梗死后左心室重构的有害作用

• 发表时间: 2012
• 作者: Xiaoxiang Yan;Motoaki Sano;Takashi Shichita;Tomohiro Matsuhashi;Yoshinori Katsumata;Akihiko Yoshimura;Keiichi Fukuda
• 通讯作者: Keiichi Fukuda

Selective Depletion of Dendritic Cells Resulted in Deteriorated Left Ventricular Remodeling after Myocardial Infarction

选择性消耗树突状细胞导致心肌梗死后左心室重构恶化

• 发表时间: 2011
• 作者: Anzai A;Anzai T;Nagai S;Maekawa Y;Kaneko H;Sugano Y;Takahashi T;Sano M;Yoshikawa T;Koyasu S;Ogawa S;Fukuda K
• 通讯作者: Fukuda K