330
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Treprostinil increases the number and angiogenic potential of endothelial progenitor cells in children with pulmonary hypertension

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Pulmonary vasodilators in general and prostacyclin therapy in particular, have markedly improved the outcome of patients with pulmonary arterial hypertension (PAH). As endothelial dysfunction is a key feature of PAH, and as endothelial progenitor cells (EPC) may contribute to vascular repair in PAH, we suspected that prostacyclin therapy might enhance EPC numbers and functions. In the present study, objectives were to determine whether EPC may contribute to vasodilator treatment efficacy in PAH.

          Methods

          We quantified CD34+ cells, CFU-Hill and ECFC (endothelial colony forming cells) in peripheral blood from children with idiopathic PAH ( n = 27) or PAH secondary to congenital heart disease ( n = 52). CD34+ were enumerated by flow cytometry, CFU-Hill and ECFC by a culture assay. ECFC grown ex vivo were tested for their angiogenic capacities before and after prostacyclin analog therapy (subcutaneous treprostinil).

          Results

          ECFC counts were significantly enhanced in the 8 children treated with treprostinil, while no change was observed in children receiving oral therapy with endothelin antagonists and/or PDE5 inhibitors. CD34+ cell and CFU-Hill counts were unaffected. ECFC from patients treated with treprostinil had a hyperproliferative phenotype and showed enhanced angiogenic potential in a nude mouse preclinical model of limb ischemia.

          Conclusions

          ECFC may partly mediate the clinical benefits of prostanoids in pulmonary arterial hypertension.

          Related collections

          Most cited references35

          • Record: found
          • Abstract: found
          • Article: not found

          A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.

          Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P < 0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P < 0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated patients. The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and +3 percent, respectively (difference in mean change, -6.7 mm Hg; 95 percent confidence interval, -10.7 to -2.6 mm Hg; P < 0.002), and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and +9 percent, respectively (difference in mean change, -4.9 mm Hg/liter/min; 95 percent confidence interval, -7.6 to -2.3 mm Hg/liter/min; P < 0.001). Eight patients died during the study, all of whom had been randomly assigned to conventional therapy (P = 0.003). Serious complications included four episodes of catheter-related sepsis and one thrombotic event. As compared with conventional therapy, the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement, as well as improved survival in patients with severe primary pulmonary hypertension.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals.

            The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies "endothelial cell colony-forming units" (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis.

              Endothelial progenitor cells (EPC) in one study group is not the same as EPC in other investigators, suggesting that EPC is not a single type of cell population. In this study, we tried to demonstrate the heterogeneity of EPC. We cultured total mononuclear cells from human peripheral blood to get two types of EPC sequentially from the same donors. We called them early EPC and late EPC. Early EPC with spindle shape showed peak growth at 2 to 3 weeks and died at 4 weeks, whereas late EPC with cobblestone shape appeared late at 2 to 3 weeks, showed exponential growth at 4 to 8 weeks, and lived up to 12 weeks. Late EPC was different from early EPC in the expression of VE-cadherin, Flt-1, KDR, and CD45. Late EPC produced more nitric oxide, incorporated more readily into human umbilical vein endothelial cells monolayer, and formed capillary tube better than early EPC. Early EPC secreted angiogenic cytokines (vascular endothelial growth factor, interleukin 8) more so than late EPC during culture in vitro. Both types of EPC showed comparable in vivo vasculogenic capacity. We found two types of EPC from a source of adult peripheral blood that might have different roles in neovasculogenesis based on the identified differences.
                Bookmark

                Author and article information

                Contributors
                +33-1-56093933 , +33-1-56093393 , david.smadja@egp.aphp.fr
                Journal
                Angiogenesis
                Angiogenesis
                Springer Netherlands (Dordrecht )
                0969-6970
                1573-7209
                4 November 2010
                4 November 2010
                March 2011
                : 14
                : 1
                : 17-27
                Affiliations
                [1 ]Université Paris Descartes, Paris, France
                [2 ]Inserm Unité 765, Faculté de Pharmacie, and AP-HP, Hôpital Européen Georges Pompidou, Haematology Department, 20 rue leblanc, 75015 Paris, France
                [3 ]AP-HP, Hôpital Européen Georges Pompidou, Pneumology Department, Paris, France
                [4 ]Vascular Biology Program, Children’s Hospital, Harvard Medical School, Boston, MA USA
                [5 ]UPRES EA4068, UFR Biomédicale des Saints Pères, Paris, France
                [6 ]Sydney Medical School, University of Sydney, Sydney, NSW 2006 Australia
                [7 ]AP-HP, Hôpital Necker-Enfants Malades, Paris, France
                Article
                9192
                10.1007/s10456-010-9192-y
                3040815
                21049284
                1239b2c6-551a-42a8-97a7-8aaa6a480c77
                © The Author(s) 2010
                History
                : 10 September 2010
                : 19 October 2010
                Categories
                Original Paper
                Custom metadata
                © Springer Science+Business Media B.V. 2011

                Human biology
                vasodilator treatment,epc,pulmonary hypertension,congenital heart disease,treprostinil

                Comments

                Comment on this article