Abstract
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.
Highlights
Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion reduces myocardial ischemia/reperfusion injury
The activation and expression of 22 signaling proteins that had previously been identified in experimental models in response to ischemic conditioning maneuvers were analyzed using Western blot analysis in left ventricular (LV) biopsies taken at early reperfusion after cardioplegic ischemic arrest from patients undergoing coronary artery bypass grafting (CABG) under isoflurane anesthesia[26, 27]
We have analyzed and compared the proteome and phosphoproteome of LV biopsies taken at early reperfusion after cardioplegic ischemic arrest from patients undergoing CABG without and with remote ischemic preconditioning (RIPC)
Summary
Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion reduces myocardial ischemia/reperfusion injury. The activation and expression of 22 signaling proteins that had previously been identified in experimental models in response to ischemic conditioning maneuvers were analyzed using Western blot analysis in left ventricular (LV) biopsies taken at early reperfusion after cardioplegic ischemic arrest from patients undergoing CABG under isoflurane anesthesia[26, 27]. Among these 22 proteins, only the activation of the signal transducer and activator of transcription 5 (STAT5) was associated with reduced biomarker release by RIPC26. This animal model has less interindividual variability than that of patients and no co-morbidities and co-medications[34]
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