Targeted deletion of regulatory T cells attenuates the protective effects of myocardial ischemic preconditioning in rats

被引:4
|
作者
Ke, Dan [1 ,2 ]
Fang, Jun [2 ]
Fan, Lin [2 ]
Chen, Lianglong [2 ]
机构
[1] Chinese Peoples Armed Police Forces, Fujian Prov Corps Hosp, Dept Cardiol, Fuzhou, Peoples R China
[2] Fujian Med Univ, Union Hosp, Fujian Inst Coronary Artery Dis, Dept Cardiol, Fuzhou 350001, Peoples R China
基金
中国国家自然科学基金;
关键词
cardioprotection; immune cell; inflammation; ischemia; reperfusion; INDUCED CARDIOPROTECTION; INJURY; ACCUMULATION; NEUTROPHILS; EXPRESSION; SUPPRESS; INCREASE;
D O I
10.3109/14017431.2015.1005661
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background. Myocardial ischemia-reperfusion injury (IRI) is associated with activation of the innate immune system and the resultant inflammatory response. Myocardial ischemic preconditioning (IPC) is the most powerful endogenous protective mechanism against myocardial IRI, probably via the role of anti-inflammation. Regulatory T cells (Tregs), which are characterized by the expression of the forkhead/winged-helix transcription factor FoxP3, play an important role in the negative modulation of immune responses. We tested the hypothesis that Tregs may contribute to the protective effect of myocardial IPC through anti-inflammatory mechanisms. Methods and results. The left anterior descending coronary arteries of rats were occluded for a 30-min ischemia, followed by a 48-h reperfusion. Myocardial IPC was induced by 4 cycles of 5-min ischemia and 5-min reperfusion. Ischemia was achieved by ligation of the left anterior descending coronary artery (LAD), and reperfusion was initiated by releasing the ligature. Rats were injected with a Treg cell-depleting antibody or normal rat immunoglobulin (IgG), after IPC. The accumulation of Tregs was observed at indexed time points following IPC. The protein expression of FoxP3 significantly increased in the myocardium after IPC, and peaked at day-2. Treatment of preconditioned rats with the Treg cell-depleting antibody demonstrated less protein expression of FoxP3 (p < 0.001), more infiltration of inflammatory cells in the myocardium (p < 0.01), and larger myocardial infarct size (p < 0.001), compared with the IgG injection group. Conclusion. Cardioprotection by IPC is associated with Tregs.
引用
收藏
页码:64 / 71
页数:8
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