Université Paris Descartes, Paris, France.
Angiogenesis. 2011 Mar;14(1):17-27. doi: 10.1007/s10456-010-9192-y. Epub 2010 Nov 4.
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.
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).
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.
ECFC may partly mediate the clinical benefits of prostanoids in pulmonary arterial hypertension.
一般来说，肺血管扩张剂，特别是前列环素治疗，显著改善了肺动脉高压（PAH）患者的预后。由于内皮功能障碍是 PAH 的一个关键特征，而内皮祖细胞（EPC）可能有助于 PAH 中的血管修复，我们怀疑前列环素治疗可能会增加 EPC 的数量和功能。在本研究中，我们的目的是确定 EPC 是否有助于 PAH 患者的血管扩张剂治疗效果。
我们从特发性 PAH 患儿（n = 27）或先天性心脏病相关 PAH 患儿（n = 52）的外周血中定量测定 CD34+细胞、CFU-Hill 和 ECFC（内皮细胞集落形成细胞）。通过流式细胞术计数 CD34+细胞，通过培养试验计数 CFU-Hill 和 ECFC。在接受前列环素类似物治疗（皮下曲前列尼尔）前后，对体外培养的 ECFC 进行其血管生成能力测试。
8 名接受曲前列尼尔治疗的患儿的 ECFC 计数显著增加，而接受内皮素拮抗剂和/或 PDE5 抑制剂口服治疗的患儿则没有变化。CD34+细胞和 CFU-Hill 计数不受影响。接受曲前列尼尔治疗的患者的 ECFC 具有过度增殖表型，并在裸鼠肢体缺血的临床前模型中显示出增强的血管生成潜力。
ECFC 可能部分介导前列环素在肺动脉高压中的临床获益。
