Remote vs. ischaemic preconditioning: the differential role of mitogen-activated protein kinase pathways

Abstract

All investigated MAPK pathways appear to be involved in RPC-induced cardioprotection; however, they do not contribute to the alterations that define the preconditioned state of the myocardium prior to the infarction.

Investigating the Signal Transduction Pathways Underlying Remote Ischemic Conditioning in the Porcine Heart

“…Importantly, the pharmacological inhibition of PI3K and Akt abrogated the infarct-limiting effects of RIPC, demonstrating that these kinases are required for cardioprotection. A previous study using the rat had already demonstrated the activation of Erk1/2 in intestinal tissue (where the conditioning stimulus was applied) but not in the heart [12]. A recent study was published which has also linked remote ischemic limb preconditioning to the activation of the PI3K-Akt pathway at reperfusion within the murine heart, although in that study the kinase inhibitor was administered prior to the remote ischemic limb preconditioning protocol rather than at reperfusion as in our study [17].…”

Protective Effect of Remote Ischemic Preconditioning in Renal Ischemia/Reperfusion Injury, in a Model of Thoracoabdominal Aorta Approach

“…The effect of RIPC is presumed to exist by humoral or neurogenic pathways. Studies have demonstrated endothelial nitric oxide [24,25], free radicals [16], kinases [26], opioids [27,28], catecholamines [29], and adenosine triphosphate sensitive potassium channels [30] as the candidates mechanism in remote preconditioning. These molecules act via the neurogenic or humoral pathway at the cellular level, resulting in transcription of new proteins, reduction of oxidative stress, and preservation of mitochondrial function.…”

Molecular Basis of Cardioprotection

“…Although there was no change in p38 expression with RIPC, 204 p38 inhibition abrogated the protection by RIPC. 205 Given the ambivalent effects of p38 isoforms, not surprisingly a clinical trial with an oral nonisoform selective inhibitor in patients with non-ST segment elevation AMI was neutral in terms of IS reduction, as reflected by troponin I release.…”