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内皮祖细胞中的性别差异与心血管风险概况:女性雌激素的作用。

Gender differences in endothelial progenitor cells and cardiovascular risk profile: the role of female estrogens.

作者信息

Fadini Gian Paolo, de Kreutzenberg Saula, Albiero Mattia, Coracina Anna, Pagnin Elisa, Baesso Ilenia, Cignarella Andrea, Bolego Chiara, Plebani Mario, Nardelli Giovanni B, Sartore Saverio, Agostini Carlo, Avogaro Angelo

机构信息

Clinical and Experimental Medicine, University of Padova Medical School, Italy.

出版信息

Arterioscler Thromb Vasc Biol. 2008 May;28(5):997-1004. doi: 10.1161/ATVBAHA.107.159558. Epub 2008 Feb 14.

DOI:10.1161/ATVBAHA.107.159558
PMID:18276910
Abstract

OBJECTIVE

Endothelial progenitor cells (EPCs) participate in vascular homeostasis and angiogenesis. The aim of the present study was to explore EPC number and function in relation to cardiovascular risk, gender, and reproductive state.

METHODS AND RESULTS

As measured by flow-cytometry in 210 healthy subjects, CD34(+)KDR(+) EPCs were higher in fertile women than in men, but were not different between postmenopausal women and age-matched men. These gender gradients mirrored differences in cardiovascular profile, carotid intima-media thickness, and brachial artery flow-mediated dilation. Moreover, EPCs and soluble c-kit ligand varied in phase with menstrual cycle in ovulatory women, suggesting cyclic bone marrow mobilization. Experimentally, hysterectomy in rats was followed by an increase in circulating EPCs. EPCs cultured from female healthy donors were more clonogenic and adherent than male EPCs. Treatment with 17beta-estradiol stimulated EPC proliferation and adhesion, via estrogen receptors. Finally, we show that the proangiogenic potential of female EPCs was higher than that of male EPCs in vivo.

CONCLUSIONS

EPCs are mobilized cyclically in fertile women, likely to provide a pool of cells for endometrial homeostasis. The resulting higher EPC levels in women than in men reflect the cardiovascular profile and could represent one mechanism of protection in the fertile female population.

摘要

目的

内皮祖细胞(EPCs)参与血管稳态和血管生成。本研究旨在探讨EPC数量及功能与心血管风险、性别和生殖状态之间的关系。

方法与结果

通过流式细胞术检测210名健康受试者,发现育龄女性的CD34(+)KDR(+) EPCs数量高于男性,但绝经后女性与年龄匹配的男性之间无差异。这些性别差异反映在心血管特征、颈动脉内膜中层厚度和肱动脉血流介导的扩张方面。此外,排卵女性的EPCs和可溶性c-kit配体随月经周期而变化,提示骨髓的周期性动员。实验中,大鼠子宫切除术后循环EPCs增加。从健康女性供体培养的EPCs比男性EPCs具有更强的克隆形成能力和贴壁能力。17β-雌二醇通过雌激素受体刺激EPC增殖和黏附。最后,我们表明女性EPCs在体内的促血管生成潜力高于男性EPCs。

结论

育龄女性的EPCs呈周期性动员,可能为子宫内膜稳态提供细胞池。女性EPC水平高于男性反映了心血管特征,并可能是育龄女性群体的一种保护机制。

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