The main pathogenic feature of preeclampsia is maternal endothelial dysfunction that results from impaired angiogenesis and reduced endothelial repair capacity. In addition, preeclampsia risk is associated with vitamin D deficiency. We hypothesized that vitamin D(3) stimulates proangiogenic properties of endothelial colony-forming cells (ECFCs). ECFCs were obtained and cultured from cord blood and characterized by immunocytochemistry and flow cytometry. Proliferation, total length of tubule formation on Matrigel, expression of VEGF mRNA, and pro-matrix metalloproteinases (MMP)-2 activity were assessed after treatment of ECFCs with vitamin D(3). Specificity of the observed effects was tested by blocking the vitamin D receptor (VDR) or the VEGF signaling pathway. ECFCs treated with 10 nM vitamin D(3) showed a 1.27 times higher tubule formation compared with vehicle-treated controls (1.27 ± 0.19) as well as a 1.36 times higher proliferation rate (1.36 ± 0.06). Vitamin D(3) induced pro-MMP-2 activity (1.29 ± 0.17) and VEGF mRNA levels (1.74 ± 0.73) in ECFCs. VDR blocking by pyridoxal-5-phosphate (0.73 ± 0.19) or small interfering RNA (0.75 ± 0.17) and VEGF inhibition by Su5416 (0.56 ± 0.16) or soluble fms-like tyrosine kinase-1 (0.7 ± 0.14) reduced tubule formation and pro-MMP-2 activity (pyridoxal-5-phosphate: 0.84 ± 0.09; Su5416: 0.79 ± 0.11; or sFlt: 0.88 ± 0.13). This effect was neutralized by vitamin D(3). Consequently, vitamin D(3) significantly promoted angiogenesis in ECFCs in vitro possibly due to an increase in VEGF expression and pro-MMP-2 activity. Since angiogenesis is a crucial feature in the pathophysiology of preeclampsia these findings could explain the positive influence of vitamin D(3) in reducing preeclampsia risk.

M. Grundmann

M. Haidar

S. Placzko

R. Niendorf

N. Darashchonak

C. A. Hubel

F. von Versen-Höynck

AJP Cell Physiology

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 致力于研究细胞和分子生理学的创新方法。使用细胞和分子方法阐明更高组织水平的生理控制机制的贡献也经常出现。鼓励涉及细胞膜、收缩系统、细胞器和膜通道、转运蛋白和泵的结构和功能的手稿。研究涉及细胞功能的综合调节，包括信号转导机制、发育、基因表达、细胞间相互作用以及病理生理状态的细胞生理学，也受到热切关注。特别欢迎将生物化学、生物物理学、分子生物学、形态学和免疫学方法应用于确定细胞生理学新原理的跨学科研究。

The American Journal of Physiology - Cell Physiology is dedicated to innovative research in cellular and molecular physiology. The journal encourages the use of cellular and molecular approaches to elucidate physiological control mechanisms at higher organizational levels. We welcome manuscripts that involve the structure and function of cell membranes, contractile systems, organelles, membrane channels, transport proteins, and pumps. Research topics include the integrated regulation of cellular functions, encompassing signal transduction mechanisms, development, gene expression, intercellular interactions, and cellular physiology in pathophysiological states. Furthermore, the journal particularly welcomes interdisciplinary studies that apply biochemistry, biophysics, molecular biology, morphology, and immunology methods to identify new principles in cellular physiology.

《American Journal of Physiology - Cell Physiology》致力于细胞和分子生理学的创新研究。期刊鼓励使用细胞和分子方法来阐明更高组织水平的生理控制机制。我们欢迎涉及细胞膜、收缩系统、细胞器、膜通道、转运蛋白和泵的结构与功能的研究手稿。研究内容包括细胞功能的综合调节，涵盖信号转导机制、发育、基因表达、细胞间相互作用以及病理生理状态下的细胞生理学。此外，期刊特别欢迎将生物化学、生物物理学、分子生物学、形态学和免疫学等方法应用于确定细胞生理学新原理的跨学科研究。

American Journal of Physiology - Cell Physiology

Vitamin D improves the angiogenic properties of endothelial progenitor cells

It is hypothesized that vitamin D(3) stimulates proangiogenic properties of endothelial colony-forming cells (ECFCs) in vitro possibly due to an increase in VEGF expression and pro-MMP-2 activity, which could explain the positive influence of vitamin D (3) in reducing preeclampsia risk.

Category	Quartile
生物学	2
生物学, 生理学	2
生物学, 细胞生物学	3

Vitamin D improves the angiogenic properties of endothelial progenitor cells

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