Proteomics/phosphoproteomics of left ventricular biopsies from patients with surgical coronary revascularization and pigs with coronary occlusion/reperfusion : remote ischemic preconditioning

Gedik, Nilgün; Krüger, Marcus; Thielmann, Matthias Klaus LSF; Kottenberg, Eva LSF; Skyschally, Andreas LSF; Frey, Ulrich H. LSF; Cario, Elke LSF; Peters, Jürgen LSF; Jakob, Heinz G. LSF; Heusch, Gerd LSF; Kleinbongard, Petra LSF

Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion reduces myocardial ischemia/reperfusion injury. In left ventricular (LV) biopsies from patients undergoing coronary artery bypass grafting (CABG), only the activation of signal transducer and activator of transcription 5 was associated with RIPC’s cardioprotection. We have now used an unbiased, non-hypothesis-driven proteomics and phosphoproteomics approach to analyze LV biopsies from patients undergoing CABG and from pigs undergoing coronary occlusion/reperfusion without (sham) and with RIPC. False discovery rate-based statistics identified a higher prostaglandin reductase 2 expression at early reperfusion with RIPC than with sham in patients. In pigs, the phosphorylation of 116 proteins was different between baseline and early reperfusion with RIPC and/or with sham. The identified proteins were not identical for patients and pigs, but in-silico pathway analysis of proteins with ≥2-fold higher expression/phosphorylation at early reperfusion with RIPC in comparison to sham revealed a relation to mitochondria and cytoskeleton in both species. Apart from limitations of the proteomics analysis per se, the small cohorts, the sampling/sample processing and the number of uncharacterized/unverifiable porcine proteins may have contributed to this largely unsatisfactory result.

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Gedik, N., Krüger, M., Thielmann, M.K., Kottenberg, E., Skyschally, A., Frey, U.H., Cario, E., Peters, J., Jakob, H.G., Heusch, G., Kleinbongard, P., 2018. Proteomics/phosphoproteomics of left ventricular biopsies from patients with surgical coronary revascularization and pigs with coronary occlusion/reperfusion: remote ischemic preconditioning. https://doi.org/10.1038/s41598-017-07883-5
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