The potential of erythropoietin for conferring cardioprotection complementing reperfusion

Abstract

EPO is promising for myocardial protection. Its potential is being delineated in a clinical study of myocardial infarction treated with tenecteplase with or without concomitant EPO.

Erythropoietin inhibits post-ischemic leukocyte adhesion but does not affect rejection in murine cardiac allografts

“…Pro-angiogenic properties of Epo, however, are most likely not responsible for acute cardioprotection, but may contribute to late remodeling. 43 Of course, qualitative and quantitative differences between cardiac and cutaneous mast cell populations may also help to explain why others found an effect of Epo on microcirculatory blood flow in the striated skin muscle. 11,12 The observed anti-inflammatory effect of Epo, that is, reduced leukocyte sequestration, did not translate into delayed allograft rejection, either with or without additional immunosuppressive cyclosporine treatment.…”

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

“…Besides its ability to increase the number of red blood cells and consequently oxygen delivery to underperfused organs, Epo has other actions that are beneficial under conditions of perfusion dysfunction, including stimulation of new blood vessel formation and a direct protective action on cells, most notably cardiac myocytes (13,93). Epo is able to protect the heart against ischemia-reperfusion injury and reduce infarct size via activation of its receptor on cardiac myocytes.…”

“…LIF (121), GH (56), Epo (77), and insulin (141) have also been reported to protect cardiac myocytes from chronic oxidative stress. Notably, a number of clinical trials have been completed or are underway assessing the efficacy of Epo or G-CSF in treating myocardial infarction and heart failure (13,87,88,93).The protective action of the type 1 receptor cytokines (see Fig. 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).…”

“…LIF (121), GH (56), Epo (77), and insulin (141) have also been reported to protect cardiac myocytes from chronic oxidative stress. Notably, a number of clinical trials have been completed or are underway assessing the efficacy of Epo or G-CSF in treating myocardial infarction and heart failure (13,87,88,93).…”

Failure of erythropoietin to render jeopardized ischemic myocardium amenable to incremental salvage by early reperfusion

“…Furthermore, increased activation of cell survival pathways, such as PI3K/Akt, MEK/ERK, and PKC, has been delineated in mice treated with EPO subjected to MI compared with that in controls subjected to MI but not administered EPO, suggesting that EPO sustains the activity of these kinases [15,22]. As a result of the apparently protective effects of EPO in preclinical studies, several clinical trials are currently in progress, including one in which our group is participating in [29][30][31].…”