Clinic of Internal Medicine I, Department of Cardiology, University Hospital Jena, Jena, Germany.
PLoS One. 2012;7(12):e52101. doi: 10.1371/journal.pone.0052101. Epub 2012 Dec 20.
Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries.
Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study.
AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG.
These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.
急性心肌梗死（AMI）后心室重构是西方国家充血性心力衰竭和死亡的主要原因。
相关报道显示，AMI 后输注凋亡白细胞或抗淋巴细胞血清可减少心肌坏死并保护心功能。为了证实这种治疗机制，本研究评估了一种具有类似机制的免疫抑制剂，如抗胸腺细胞球蛋白（ATG）的作用。
通过结扎左前降支在大鼠中诱导 AMI。AMI 发生后立即静脉注射兔 ATG（10mg/只）。体外和体内实验表明，ATG 可引起促血管生成和趋化因子的显著释放。此外，与 ATG 共孵育的细胞培养物释放的旁分泌因子可下调心肌细胞中的 p53。用 ATG 注射的大鼠缺血心肌中 CD68+巨噬细胞数量增加。用 ATG 注射的动物心肌坏死程度较低，6 周后梗死面积明显减少，AMI 后重构得到改善（梗死面积 24.9%比 11.4%，p<0.01）。此外，在梗死周围区域有更高的血管密度表明用 ATG 注射的大鼠有更好的侧支循环。
这些数据表明，ATG 是一种在临床移植免疫中成功应用的治疗药物，在 AMI 后触发了心脏保护作用，通过下调 p53 挽救了缺血心肌。这可能提高了缺血期间细胞凋亡的抵抗能力。这些机制的结合可能是实验性 AMI 后心功能改善和心室重构减少的原因。
