Abstract
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.
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Research conducted in authors’ laboratories is supported by the institutional funds of Scuola Superiore Sant’Anna (Pisa, Italy; V.L.), G. Pasquinucci Heart Hospital, Gabriele Monasterio Foundation (Massa, Italy; M.S.), and Division of Cardiac Surgery, University of Bari “Aldo Moro” (Bari, Italy; D.P.). Funding source had no such involvement in study design, in the collection, analysis, interpretation of data, in the writing of the report, and in the decision to submit the paper for publication.
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AC and VL conceived and designed research. AC, FB, EDN, NS, GP, and SS conducted the experiments. VC, DDS, GS, and VL analyzed data and interpreted the results of the experiments. MS, PM, DP, and VL drafted the manuscript. All authors edited, revised, and approved the final version of the manuscript.
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Carrozzo, A., Casieri, V., Di Silvestre, D. et al. Plasma exosomes characterization reveals a perioperative protein signature in older patients undergoing different types of on-pump cardiac surgery. GeroScience 43, 773–789 (2021). https://doi.org/10.1007/s11357-020-00223-y
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DOI: https://doi.org/10.1007/s11357-020-00223-y