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Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner.
Cardiovasc Res. 2005 Nov 01; 68(2):299-306.CR

Abstract

OBJECTIVES

Patients with congestive heart failure (CHF) suffer considerable morbidity and mortality despite advances in therapy. Treatment with erythropoietin (Epo) has shown promise in CHF patients, yet its mechanisms of action remain elusive. Endothelial progenitor cells (EPC) contribute to postnatal angiogenesis and vasculogenesis, and Epo was shown to promote EPC mobilization. We explored the effect of chronic treatment with Epo on the numbers and functional properties of EPC in CHF patients.

METHODS AND RESULTS

Twenty-eight patients with CHF treated with Epo for a mean period of 28 months were compared to a matched group (n = 28) with regard to the number of circulating hematopoietic and endothelial stem cells (either CD34+, CD34+/CD45+, CD34+/CD133+, CD34+/VEGF-R2+ or CD34+/CD133+/VEGF-R2+) as well as their proliferative and adhesive capacity. In vitro, Epo was added to cultured EPC from healthy subjects to test proliferation and adhesion. No differences were observed in circulating numbers of hematopoietic and endothelial stem cells between CHF patients chronically treated with Epo or untreated. EPC from Epo-treated patients exhibited enhanced proliferation as well as a trend towards adhesion to cultured endothelial cells prior to and following stimulation with TNF-alpha. Addition of Epo to EPC from healthy subjects dose-dependently increased their proliferation and adhesion to fibronectin, cultured endothelial cells, and cardiomyocytes. These effects were significantly reduced in the presence of phosphatidylinositol (PI) 3-kinase inhibitors.

CONCLUSIONS

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

Authors+Show Affiliations

The Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Israel. jacobg@post.tau.ac.ilNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16048724

Citation

George, Jacob, et al. "Erythropoietin Promotes Endothelial Progenitor Cell Proliferative and Adhesive Properties in a PI 3-kinase-dependent Manner." Cardiovascular Research, vol. 68, no. 2, 2005, pp. 299-306.
George J, Goldstein E, Abashidze A, et al. Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner. Cardiovasc Res. 2005;68(2):299-306.
George, J., Goldstein, E., Abashidze, A., Wexler, D., Hamed, S., Shmilovich, H., Deutsch, V., Miller, H., Keren, G., & Roth, A. (2005). Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner. Cardiovascular Research, 68(2), 299-306.
George J, et al. Erythropoietin Promotes Endothelial Progenitor Cell Proliferative and Adhesive Properties in a PI 3-kinase-dependent Manner. Cardiovasc Res. 2005 Nov 1;68(2):299-306. PubMed PMID: 16048724.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner. AU - George,Jacob, AU - Goldstein,Emil, AU - Abashidze,Anastasia, AU - Wexler,Dov, AU - Hamed,Saher, AU - Shmilovich,Haim, AU - Deutsch,Varda, AU - Miller,Hylton, AU - Keren,Gad, AU - Roth,Arie, Y1 - 2005/07/26/ PY - 2005/04/25/received PY - 2005/06/06/revised PY - 2005/06/17/accepted PY - 2005/7/29/pubmed PY - 2006/3/11/medline PY - 2005/7/29/entrez SP - 299 EP - 306 JF - Cardiovascular research JO - Cardiovasc Res VL - 68 IS - 2 N2 - OBJECTIVES: Patients with congestive heart failure (CHF) suffer considerable morbidity and mortality despite advances in therapy. Treatment with erythropoietin (Epo) has shown promise in CHF patients, yet its mechanisms of action remain elusive. Endothelial progenitor cells (EPC) contribute to postnatal angiogenesis and vasculogenesis, and Epo was shown to promote EPC mobilization. We explored the effect of chronic treatment with Epo on the numbers and functional properties of EPC in CHF patients. METHODS AND RESULTS: Twenty-eight patients with CHF treated with Epo for a mean period of 28 months were compared to a matched group (n = 28) with regard to the number of circulating hematopoietic and endothelial stem cells (either CD34+, CD34+/CD45+, CD34+/CD133+, CD34+/VEGF-R2+ or CD34+/CD133+/VEGF-R2+) as well as their proliferative and adhesive capacity. In vitro, Epo was added to cultured EPC from healthy subjects to test proliferation and adhesion. No differences were observed in circulating numbers of hematopoietic and endothelial stem cells between CHF patients chronically treated with Epo or untreated. EPC from Epo-treated patients exhibited enhanced proliferation as well as a trend towards adhesion to cultured endothelial cells prior to and following stimulation with TNF-alpha. Addition of Epo to EPC from healthy subjects dose-dependently increased their proliferation and adhesion to fibronectin, cultured endothelial cells, and cardiomyocytes. These effects were significantly reduced in the presence of phosphatidylinositol (PI) 3-kinase inhibitors. CONCLUSIONS: Chronic Epo treatment is associated with an increase in the adhesive and proliferative properties of circulating EPC in patients with CHF. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/16048724/Erythropoietin_promotes_endothelial_progenitor_cell_proliferative_and_adhesive_properties_in_a_PI_3_kinase_dependent_manner_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1016/j.cardiores.2005.06.022 DB - PRIME DP - Unbound Medicine ER -