Erythropoietin protects post-ischemic hearts by preventing extracellular matrix degradation: Role of Jak2-ERK pathway

Erythropoietin Attenuates Hyperoxia-Induced Cell Death by Modulation of Inflammatory Mediators and Matrix Metalloproteinases

“…Moreover, in an in vitro setting, rEpo-activated endothelial cells enhance neural progenitor cell migration by secreting MMP-2 and MMP-9 via phosphatidylinositol 3-kinase (Akt) and Jak2/ERK1/2 signaling pathways [31] . rEpo treatment was shown to be protective in ischemic heart injury by attenuating extracellular matrix degradation mediated by MMP-2 and MMP-9 via enhancement of ERK phosphorylation [32] . As a growth factor, binding to its receptor leads to phosphorylation of stress-responsive Jak2 and this recruits multiple signaling cascades, including MAPK [18] .…”

JAK redux: a second look at the regulation and role of JAKs in the heart

“…Of note, leptin treatment preserved systolic function but caused eccentric dilatation of the heart. A number of studies either in vivo or on isolated hearts have demonstrated that Epo delivered acutely during ischemia or reperfusion or chronically after MI reduces infarct size, oxidative stress, inflammation, and apoptosis and improves cardiac function (20,96,136,138). Thrombopoietin (Tpo), another class I hematopoietic cytokine that shares sequence homology with Epo, was shown to preserve cardiac structure and function when given before ischemia-reperfusion assault of the rat heart and to reduce infarct size when given at the onset of ischemia or at reperfusion (8).…”

“…91) erythropoietin (Epo; Refs. 20,134,138), and granulocyte colony-stimulating factor (G-CSF; Refs. 26,61,62,72,159,166), as well as insulin (3,23,54,64,99,164,186), have been shown to protect the heart from acute oxidative stress, viz., ischemia-reperfusion injury.…”

“…1 for IL-6 cytokine signaling) and insulin has been shown to involve activation of two intracellular signaling cascades: 1) the reperfusion injury salvage kinase (RISK) pathway (17,27,40,41,64,66,77,99,101,102,108,121,126,128,133,134,142,156,159,160,161,166) and 2) JAK-STAT signaling (20,40,61,85,161,174). The former, which involves the sequential activation of phosphatidylinositol 3-kinase (PI3-kinase) and AKT, as well as ERK1/2, has as a major target inhibition of the mitochondrial permeability transition pore (MPTP) and plays a dominant role in the mediator phase of both early (classical) preconditioning and postconditioning of the heart (29,164).…”

Erythropoietin alleviates post-ischemic injury of rat hearts by attenuating nitrosative stress

“…We previously reported that the administration of recombinant human erythropoietin (EPO) to isolated perfused hearts, or endogenous induction of EPO by exposing rats to chronic hypoxia, protects hearts against IR injury (Chan et al, 2007;Lin et al, 2008). EPO exerts its effects by binding to the EPO receptor, which is present in cardiomyocytes (Jones et al, 1991;Lin et al, 2008).…”