Abstract

Remote ischemic preconditioning’s (RIPC) ability to render the myocardium resistant to subsequent prolonged ischemia is now clearly established in different species, including humans. Strong evidence suggests that circulating humoral mediators play a key role in signal transduction, but their identities still need to be established. Our study sought to identify potential circulating RIPC mediators using a proteomic approach. Rats were exposed to 10-min limb ischemia followed by 5- (RIPC 5′) or 10-min (RIPC 10′) reperfusion prior to blood sampling. The control group only underwent blood sampling. Plasma samples were isolated for proteomic analysis using surface-enhanced laser desorption and ionization - time of flight - mass spectrometry (SELDI-TOF-MS). A total of seven proteins, including haptoglobin and transthyretin, were detected as up- or down-regulated in response to RIPC. These proteins had previously been identified as associated with organ protection, anti-inflammation, and various cellular and molecular responses to ischemia. In conclusion, this study indicates that RIPC results in significant modulations of plasma proteome.

Highlights

  • First described in 1986 by Murry et al [1], ischemic preconditioning (IPC) is a powerful technique, consisting of short periods of coronary artery ischemia-reperfusion (I/R), that attenuate I/R injuries caused by subsequent prolonged coronary occlusion

  • Scattergram showing the significant differences in intensity of 8317 m/z peak in plasma samples derived from Control, remote ischemic preconditioning (RIPC) 59, and RIPC 109 rats

  • Our data shows that RIPC by a short episode of limb I/R in vivo was highly related to proteomic modulation, with up- and downregulation of plasma protein expression

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Summary

Introduction

First described in 1986 by Murry et al [1], ischemic preconditioning (IPC) is a powerful technique, consisting of short periods of coronary artery ischemia-reperfusion (I/R), that attenuate I/R injuries caused by subsequent prolonged coronary occlusion. Many experimental studies have explored another preconditioning method, applicable to most patients: remote ischemic preconditioning (RIPC) This is a phenomenon whereby transient ischemia of a tissue or an organ at a distance from the heart affords cardioprotection when applied before myocardial I/R [4]. RIPC, which uses a standard blood pressure cuff placed around the arm, has emerged as an attractive non-invasive strategy in clinical settings [8,9] This approach has been taken in several clinical trials, and has been shown to be effective in patients undergoing corrective cardiac surgery for congenital heart disease [10], coronary bypass surgery [11,12], elective surgery for abdominal aortic aneurysm [13], or elective percutaneous coronary intervention (PCI) [14]

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