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

Smadja DM, Mauge L, Gaussem P, d'Audigier C, Israel-Biet D, Celermajer DS, Bonnet D, Lévy M - Angiogenesis (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Université Paris Descartes, Paris, France. david.smadja@egp.aphp.fr

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.

Show MeSH

Related in: MedlinePlus

HPC, CFU-Hill and ECFC counts in peripheral venous blood of patients with pulmonary hypertension, with and without treatment. a Number of CD34+ hematopoietic progenitor cells (HPC) determined by FACS analysis according to patient group. No difference is observed between the treated and non treated patients (P = 0.80). b Number of CFU-Hill colonies determined by cell culture according to patient group. No difference is observed between the treated and non treated patients (P = 0.89). c Number of ECFC determined by cell culture according to patient group. No difference is observed between the treated and non treated patients (P = 0.15)
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3040815&req=5

Fig2: HPC, CFU-Hill and ECFC counts in peripheral venous blood of patients with pulmonary hypertension, with and without treatment. a Number of CD34+ hematopoietic progenitor cells (HPC) determined by FACS analysis according to patient group. No difference is observed between the treated and non treated patients (P = 0.80). b Number of CFU-Hill colonies determined by cell culture according to patient group. No difference is observed between the treated and non treated patients (P = 0.89). c Number of ECFC determined by cell culture according to patient group. No difference is observed between the treated and non treated patients (P = 0.15)

Mentions: No significant change in HPC, CFU-Hill and ECFC were observed when all treated patients versus non treated patients were compared (Fig. 2a, b, c respectively, with P = 0.80, 0.89 and 0.15). Oral treatment (monotherapy or bitherapy) did not modify HPC, CFU-Hill and ECFC counts count (respectively, P = 0.52, 0.64 and 0.22, Fig. 3). No change in HPC or CFU-Hill counts (P = 0.76 and P = 0.19, respectively, Fig. 3a, b) were observed after prostanoid therapy (SC treprostinil), while in contrast, this led to a significant increase in ECFC counts (P = 0.04, Fig. 3c).Fig. 2


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

Smadja DM, Mauge L, Gaussem P, d'Audigier C, Israel-Biet D, Celermajer DS, Bonnet D, Lévy M - Angiogenesis (2010)

HPC, CFU-Hill and ECFC counts in peripheral venous blood of patients with pulmonary hypertension, with and without treatment. a Number of CD34+ hematopoietic progenitor cells (HPC) determined by FACS analysis according to patient group. No difference is observed between the treated and non treated patients (P = 0.80). b Number of CFU-Hill colonies determined by cell culture according to patient group. No difference is observed between the treated and non treated patients (P = 0.89). c Number of ECFC determined by cell culture according to patient group. No difference is observed between the treated and non treated patients (P = 0.15)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040815&req=5

Fig2: HPC, CFU-Hill and ECFC counts in peripheral venous blood of patients with pulmonary hypertension, with and without treatment. a Number of CD34+ hematopoietic progenitor cells (HPC) determined by FACS analysis according to patient group. No difference is observed between the treated and non treated patients (P = 0.80). b Number of CFU-Hill colonies determined by cell culture according to patient group. No difference is observed between the treated and non treated patients (P = 0.89). c Number of ECFC determined by cell culture according to patient group. No difference is observed between the treated and non treated patients (P = 0.15)
Mentions: No significant change in HPC, CFU-Hill and ECFC were observed when all treated patients versus non treated patients were compared (Fig. 2a, b, c respectively, with P = 0.80, 0.89 and 0.15). Oral treatment (monotherapy or bitherapy) did not modify HPC, CFU-Hill and ECFC counts count (respectively, P = 0.52, 0.64 and 0.22, Fig. 3). No change in HPC or CFU-Hill counts (P = 0.76 and P = 0.19, respectively, Fig. 3a, b) were observed after prostanoid therapy (SC treprostinil), while in contrast, this led to a significant increase in ECFC counts (P = 0.04, Fig. 3c).Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Université Paris Descartes, Paris, France. david.smadja@egp.aphp.fr

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.

Show MeSH
Related in: MedlinePlus