Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner

George, Jacob; Goldstein, Emil; Abashidze, Anastasia; Wexler, Dov; Hamed, Saher; Shmilovich, Haim; Deutsch, Varda; Miller, Hylton I.; Keren, Gad; Roth, Arie

doi:10.1016/j.cardiores.2005.06.022

Cited by 113 publications

(87 citation statements)

References 36 publications

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“…There is long-standing evidence that expression of erythropoietin receptors is not restricted to erythroid precursors in the marrow but is also detectable in nonerythroid tissues, including neurons, adipocytes, and vascular endothelium (37). There is also evidence that erythropoietin affects vascular endothelial function and influences angiogenesis (38)(39)(40)(41)(42). Hence, nonerythropoietic effects of epoetin, particularly at high pharmacologic blood levels, could have a role in promoting adverse clinical events associated with epoetin treatment in patients with kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States

Wright¹,

Wright

Narva

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Recombinant human erythropoietin (epoetin) is used routinely to increase blood hemoglobin levels in patients with ESRD and anemia. Although lower doses of epoetin are required to achieve equivalent hemoglobin responses when administered subcutaneously rather than intravenously, standard practice has been to administer epoetin to patients on hemodialysis intravenously. Randomized trials of alternative epoetin treatment regimens in patients with kidney failure have shown that risks of cardiovascular complications and death are related to the dose levels of epoetin used. Therefore, given the dose-sparing advantages of subcutaneous epoetin administration, the possibility that treatment of patients on hemodialysis with subcutaneous epoetin might be associated with more favorable outcomes compared with intravenous treatment was investigated.Design, setting, participants, & measurements A retrospective cohort study of 62,710 adult patients on hemodialysis treated with either intravenous or subcutaneous epoetin-a and enrolled in the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project from 1997 to 2005 was carried out. Risks of death and/or hospitalization for cardiovascular complications (adverse composite event outcomes) during 2 years of follow-up were determined in relationship to epoetin dose and route of administration (intravenous versus subcutaneous) by multivariate Cox proportional hazard modeling adjusted for demographics and clinical parameters.Results Epoetin doses used to achieve equivalent hemoglobin responses in study patients were, on average, 25% higher when epoetin was administered intravenously rather than subcutaneously (as expected). Moreover, adverse composite event outcomes were found to be significantly more likely to occur during follow-up for patients on hemodialysis managed with intravenous rather than subcutaneous epoetin (adjusted hazard ratio for adverse events within 1 year [intravenous versus subcutaneous] was 1.11 [95% confidence interval, 1.04 to 1.18]).Conclusions This study finds that treatment of patients on hemodialysis with subcutaneous epoetin is associated with more favorable clinical outcomes than those associated with intravenous epoetin treatment.

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Section: Discussionmentioning

confidence: 99%

Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States

Wright¹,

Wright

Narva

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Even treatment with erythropoietin seems to have beneficial effects on the functional properties of EPCs in both animals and humans [30] , while a study of Iwakura and colleagues showed an increase in the mobilization of EPCs after treatment with estradiol [31] .…”

Section: Endothelium Dysfunction and Cardiovascular Diseases: Role Ofmentioning

confidence: 99%

Nutraceuticals and cardiovascular risk: potential role of EPCs modulation

Russo

Lucchesi

Longo

et al. 2015

Stem Cell Transl Investig

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According to WHO cardiovascular diseases (CVDs) are the first cause of death in the world: more people die annually from CVDs than from any other cause. Vascular endothelium plays a pivotal role in the onset and progression of these pathologies and cardiovascular risk factors are frequently associated to the levels of endothelial progenitor cells (EPCs), bone marrow-derived circulating progenitors for the endothelial lineage. Since EPCs not only preserve vascular endothelium homeostasis, but might directly participate to re-endothelization and neovascularization, these cells represent an emerging protagonist in vascular competency and as such a cell model of great interest. An unhealthy diet is one of the main cardiovascular risk factor, while there is a great interest in the potential protective effects of "nutraceuticals", food-derived compounds that exert beneficial effects on human and animal health. The characterization of the endothelial effects of different nutraceuticals may provide fresh insights into their potential role in CVDs prevention. Several studies have already showed the protective effects of natural antioxidants on EPCs levels and functionality; some examples are resveratrol, catechin and folic acid. Fermentation has recently shown interesting roles in cardiovascular prevention since this process gave origin to a new class of foods, rich in bioactive compounds, the fermented foods. Consumption of fermented legumes and cereals, but also fermented beverages (such as beer and wine) was found to protect endothelial function through both lipid-lowering, as well anti-inflammatory and antioxidative mechanisms. Little is known about the effects of fermentation-derived nutraceuticals on EPCs. Given the important role of this cardiovascular biomarker, further analysis in this field can improve opportunities for CVDs prevention and treatment. Vascular endothelium and EPCs: new insightsFor many years vascular endothelium has been considered a mere physical barrier between blood and underlying tissues; recent studies have demonstrated new and interesting roles of endothelium in vascular health [1] .Endothelial cells composing this monolayer have therefore paracrine, endocrine and autocrine functions, by secreting several factors with vasodilatory and antiproliferative effects, such as endothelium-derived hyperpolarization factor (EDHF), nitric oxide (NO) and prostacyclin (PGI 2 ), and others inducing vasoconstrictor response, for instance endothelin-1 (ET-1), angiotensin II and reactive oxygen species (ROS) [2] . These evidences make the vascular endothelium a multifunctional unit that regulates vascular homeostasis by REVIEW

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“…8 Although possible EPO production in renal tubular cells was reported previously 9, 10 a more recent study has shown that fibroblast-like cells in the corticomedullary interstitium of the kidney synthesize EPO, while tubular cells do not. 8 Proliferative effect of EPO on several progenitor cells including erythroid progenitor cells, [11][12][13] endothelial progenitor cells (EPC), 14,15 cardiomyogenic stem cells 37 has been reported. EPO is known to act specifically on haematopoietical cells, however recent evidence demonstrated several non-haematopoietical effects.…”

Section: Introductionmentioning

confidence: 99%

“…Stimulation of cultured endothelial cells with rHuEPO resulted in cell proliferation and differentiation into vascular structures. 15 George et al 14 reported that EPC proliferative effect of EPO is dose dependent, it was evident at low doses such as 1 U/ml and lost at higher doses such as 25 U/ml. Moreover, addition of EPO, dose dependently increased EPC adhesion to fibronectin, cultured endothelial cells and cardiomyocytes.…”

Section: Introductionmentioning

confidence: 99%

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Erythropoietin and Cardiovascular System

Güven¹,

Tarihi

2012

BSBD

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bsbd@balikesir.edu.tr www.bau-sbdergisi.com ÖZET Eritropoetin (EPO), sağlıklı bireylerde kemik iliğinde normal eritrosit üretimi için gerekli olan bir glikoprotein hormondur. Hipoksik koşullar altında eritropoezi indükler. Renal peritübüler hücrelerden ve karaciğer, dalak, akciğer, beyin, kemik iliği, üreme organları gibi farklı ekstrarenal dokulardan salınır. EPO ile reseptörünün (EPO-R) etkileşimi, eritroid progenitör hücrelerin programlanmış hücre ölümünü (apopitozis) azaltır ve bu hücrelerin kemik iliğinde farklılaşmasını teşvik eder. Klinik olarak, rHuEPO (rekombinant insan EPO) kronik böbrek yetmezliği sonucu gelişen EPO eksikliğine bağlı anemi tedavisinde 1980'lerin sonlarından beri kullanılmaktadır. EPO-R, eritroid progenitor hücrelerin yanı sıra, nöronlar, endotel hücreleri, vasküler düz kas hücreleri ve kalp kası hücreleri gibi çeşitli hücre gruplarında da eksprese edilir. EPO nun kalp, böbrekler, retina, karaciğer, akciğer, bağırsaklar ve beyinde hipoksi ve iskemireperfüzyon hasarına karşı sitoprotektif etkiye sahip olduğu gösterilmiştir. EPO'nun temel sitoprotektif etkisinin iskemik/hipoksik dokuda apopitozisi inhibe etmek olduğu öne sürülmüştür. Apopitozisin inhibisyonu yanı sıra, EPO doğrudan ya da dolaylı olarak hücreleri koruyan pek çok farklı etki de göstermektedir. Bu nedenle EPO genel doku koruyucu bir sitokin olarak değerlendirilmelidir.Anahtar Kelimeler: Eritropoetin, kök hücre, kardiyovasküler sistem SUMMARY Erythropoietin (EPO) is a glycoprotein hormone which is essential for normal erythrocyte production in bone marrow in healthy subjects. It induces erythropoiesis under hypoxic conditions. It is released from renal peritubular cells and various extrarenal tissues like liver, spleen, brain, lungs, bone marrow, reproductive organs. Interaction of EPO with its receptor (EPO-R) decreases programmed death (apoptosis) of erythroid progenitor cells and promotes their differentiation in bone marrow. Clinically, rHuEPO (recombinant human EPO) has been used since the late 1980s in patients with anaemia due to EPO deficiency as a consequence of chronic renal failure. In addition to erythroid progenitor cells, a varied group of cells including neurons, endothelial cells, vascular smooth muscle cells, and cardiac myocytes express EPO-R. It has been shown that Epo has cytoprotective properties against ischemia reperfusion damage and hypoxia in the brain, heart, kidneys, retina, liver, lungs, and intestines. It was suggested that inhibition of apoptosis in ischemic/hypoxic tissue is the major cytoprotective effect of EPO. In addition to inhibition of apoptosis, EPO exhibits many other actions that serve to protect cells either directly or indirectly. EPO should therefore be regarded also as a general tissueprotective cytokine.

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Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner

Abstract: Chronic Epo treatment is associated with an increase in the adhesive and proliferative properties of circulating EPC in patients with CHF.

Cited by 113 publications

References 36 publications

Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States

Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States

Nutraceuticals and cardiovascular risk: potential role of EPCs modulation

Erythropoietin and Cardiovascular System

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