Ciulla Michele M, Giorgetti Alessandra, Silvestris Ilaria, Cortiana Michela, Montelatici Elisa, Paliotti Roberta, Annoni Giuseppe A, Fiore Anna Valeria, Giordano Rosaria, De Marco Federico, Magrini Fabio, Rebulla Paolo, Cortelezzi Agostino, Lazzari Lorenza
Istituto di Medicina Cardiovascolare, Centro di Fisiologia Clinica e Ipertensione, Università di Milano, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, IRCCS, Italy.
Curr Neurovasc Res. 2006 May;3(2):99-106. doi: 10.2174/156720206776875876.
The majority of clinical studies on endothelial progenitor cells (EPCs) focuses on the role of these cells in cardiovascular diseases and no systematic studies exist regarding their variations in healthy subjects. In order to define the burden of angiogenesis in physiological conditions we assessed the frequency of peripheral blood endothelial colonies (PB-ECs) and their relation with other factors possibly involved in their function such as high-sensitivity C-reactive protein (hs-CRP), endothelial cell-specific mitogen factor (VEGF) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in a highly selected healthy population. A PB sample was obtained from 37/47 healthy subjects (age 40.2+/-15.0yrs; M/F 15/22) without known cardiovascular risk factors. The serum level of hs-CRP, VEGF, TIMP-1, the frequency of PB-ECs by clonogenic assay, and the number of early EPCs and late EPCs by flow cytometry analysis were evaluated. PB-ECs were formed by 40.5% of studied subjects with a mean of 0.40+/-0.82 colonies/10(6) cells. The differences in the frequency of colony formation between genders were not statistically significant. The subjects with PB-ECs were characterized by higher values of hs-CRP, when compared with those not forming colonies, 0.276+/-0.230 vs 0.095+/-0.077 mg/l (p=0.003) respectively, and of VEGF, 328.3+/-162.9 vs 202.68+/-118.53 pg/ml (p=0.02). No significant differences were found in TIMP-1 values. The EPC clonogenic potential seems to be related to hs-CRP and VEGF levels even in healthy population supporting the concept that these mediators are involved in physiological ECs function.
大多数关于内皮祖细胞（EPCs）的临床研究都集中在这些细胞在心血管疾病中的作用，而对于健康受试者中它们的变化情况尚无系统性研究。为了确定生理条件下血管生成的负荷，我们在一个经过严格筛选的健康人群中评估了外周血内皮集落（PB-ECs）的频率及其与其他可能参与其功能的因素的关系，这些因素包括高敏C反应蛋白（hs-CRP）、内皮细胞特异性促有丝分裂因子（VEGF）和金属蛋白酶组织抑制剂-1（TIMP-1）。从37/47名无已知心血管危险因素的健康受试者（年龄40.2±15.0岁；男/女15/22）中采集了外周血样本。评估了hs-CRP、VEGF、TIMP-1的血清水平，通过克隆形成试验评估PB-ECs的频率，以及通过流式细胞术分析评估早期EPCs和晚期EPCs的数量。40.5%的研究对象形成了PB-ECs，平均为0.40±0.82个集落/10(6)个细胞。性别之间集落形成频率的差异无统计学意义。与未形成集落的受试者相比，形成PB-ECs的受试者hs-CRP值更高，分别为0.276±0.230 vs 0.095±0.077 mg/l（p=0.003），VEGF值也更高，为328.3±162.9 vs 202.68±118.53 pg/ml（p=0.02）。TIMP-1值未发现显著差异。即使在健康人群中，EPC的克隆形成潜力似乎也与hs-CRP和VEGF水平有关，这支持了这些介质参与生理性内皮细胞功能的概念。
