There are three major signalling cascades of protein kinase activation in cardioprotection: (A) the GPCR/NPR-AKT-eNOS-PKG pathway, (B) the reperfusion-injury salvage kinase (RISK) pathway, and (C) the survival activating factor enhancement (SAFE) pathway, which centrally involves gp130-JAK-STAT signalling. In each system, there are molecules that are decreased in expression and/or activity with advancing age (marked in yellow) and possibly contribute to the loss of cardioprotection with aging. Such loss of cardioprotection with aging is one major problem in the translation of experimental data from (usually young and healthy) animals to the clinical situation in elderly humans.
Abbreviations: AMPK, AMP-activated kinase; ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; CB-R, cannabinoid receptor; Cx43, connexin 43; eNOS, endothelial NO synthase; ERK, extracellular regulated kinase; FGF-2, fibroblast growth factor 2; gp130, glycoprotein 130; GPCR, G-protein-coupled receptor; GSK3β, glycogen synthase kinase 3 β; H11K, H11 kinase; IGF, insulin-like growth factor 1; IL-6, interleukin 6; iNOS, inducible NO synthase; JAK, janus kinase; KATP, ATP-dependent potassium channel, MnSOD, manganese superoxide dismutase; MPTP, mitochondrial permeability transition pore; NO, nitric oxide; NPR, natriuretic peptide receptor; p38, p38 mitogen activated protein kinase; P70S6K, p70 ribsosomal S6 protein kinase; pGC, particulate guanylyl cyclase; PI3K, phosphoinositide 3-kinase; PKC, protein kinase C; PKG, protein kinase G; ROS, reactive oxygen species; sGC, soluble guanylyl cyclase; SIRT1, sirtuin 1; STAT3, signal transducer and activator of transcription 3; TNF-R, tumour necrosis factor receptor; UCN, urocortins.
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