Although exosomes are extracellular nanovesicles mainly involved in cardioprotection, it is not known whether plasma exosomes of older patients undergoing different types of on-pump cardiac surgery protect cardiomyocytes from apoptosis. Since different exosomal proteins confer pro-survival effects, we have analyzed the protein cargo of exosomes circulating early after aortic unclamping. Plasma exosomes and serum cardiac troponin I levels were measured in older cardiac surgery patients (NYHA II-III) who underwent first-time on-pump coronary artery bypass graft (CABG; n = 15) or minimally invasive heart valve surgery (mitral valve repair, n = 15; aortic valve replacement, n = 15) at induction of anesthesia (T0, baseline), 3 h (T1) and 72 h (T2) after aortic unclamping. Anti-apoptotic role of exosomes was assessed in HL-1 cardiomyocytes exposed to hypoxia/re-oxygenation (H/R) by TUNEL assay. Protein exosomal cargo was characterized by mass spectrometry approach. Exosome levels increased at T1 (P < 0.01) in accord with troponin values in all groups. In CABG group, plasma exosomes further increased at T2 (P < 0.01) whereas troponin levels decreased. In vitro, all T1-exosomes prevented H/R-induced apoptosis. A total of 340 exosomal proteins were identified in all groups, yet 10% of those proteins were unique for each surgery type. In particular, 22 and 12 pro-survival proteins were detected in T1-exosomes of heart valve surgery and CABG patients, respectively. Our results suggest that endogenous intraoperative cardioprotection in older cardiac surgery patients is early mediated by distinct exosomal proteins regardless of surgery type.

尽管外泌体是主要参与心脏保护的细胞外纳米囊泡，但尚不清楚接受不同类型体外循环心脏手术的老年患者的血浆外泌体是否可以保护心肌细胞免于凋亡。由于不同的外泌体蛋白具有促生存作用，因此我们分析了主动脉钳夹后早期循环的外泌体的蛋白质货物。测量了首次接受体外循环冠状动脉旁路移植术 (CABG; n = 15) 或微创心脏瓣膜手术（二尖瓣修复术）的老年心脏手术患者 (NYHA II-III) 的血浆外泌体和血清心肌肌钙蛋白I 水平，n  = 15；主动脉瓣置换术，n  = 15）在麻醉诱导（T0，基线）、主动脉松开后 3 小时（T1）和 72 小时（T2）时。通过 TUNEL 测定评估暴露于缺氧/复氧 (H/R) 的 HL-1 心肌细胞中外泌体的抗凋亡作用。蛋白质外泌体货物通过质谱方法进行表征。T1 时外泌体水平增加（P  < 0.01），与所有组中的肌钙蛋白值一致。在CABG组中，T2时血浆外泌体进一步增加（P  <0.01），而肌钙蛋白水平下降。在体外，所有 T1 外泌体都能阻止 H/R 诱导的细胞凋亡。所有组中总共鉴定出 340 种外泌体蛋白，但其中 10% 的蛋白对于每种手术类型都是独特的。特别是，在心脏瓣膜手术和 CABG 患者的 T1 外泌体中分别检测到 22 种和 12 种促生存蛋白。我们的结果表明，无论手术类型如何，老年心脏手术患者的内源性术中心脏保护都是由不同的外泌体蛋白早期介导的。