Vitamin D improves the angiogenic properties of endothelial progenitor cells
Vitamin D improves the angiogenic properties of endothelial progenitor cells
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DOI：
10.1152/ajpcell.00030.2012
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发表时间：
2012-11-01
影响因子：
5.5
通讯作者：
von Versen-Hoeynck, F.
中科院分区：
文献类型：
--
作者：
Grundmann, M.;Haidar, M.;von Versen-Hoeynck, F.
张建军，张建军，张建军，等。维生素D对内皮祖细胞血管生成的影响。[J] .中国生物医学工程学报，2016,31(2):559 - 564。首次发表于2012年8月29日；doi: 10.1152 / ajpcell.00030.2012。子痫前期的主要致病特征是母体内皮功能障碍，这是由血管生成受损和内皮修复能力降低引起的。此外，子痫前期风险与维生素D缺乏有关。我们假设维生素D-3刺激内皮集落形成细胞（ecfc）的促血管生成特性。从脐带血中获得并培养ecfc，并采用免疫细胞化学和流式细胞术对其进行表征。用维生素D-3治疗ecfc后，观察其增殖、基质小管形成总长度、VEGF mRNA表达和前基质金属蛋白酶(MMP)-2活性。通过阻断维生素D受体（VDR）或VEGF信号通路来检测观察到的效果的特异性。10 nM维生素D-3处理的ecfc的小管形成率是对照的1.27倍（1.27 +/- 0.19），增殖率是对照的1.36倍（1.36 +/- 0.06）。维生素D-3诱导ecfc中pro-MMP-2活性（1.29 +/- 0.17）和VEGF mRNA水平（1.74 +/- 0.73）。吡哆醛-5-磷酸（0.73 +/- 0.19）或小干扰RNA（0.75 +/- 0.17）阻断VDR， Su5416（0.56 +/- 0.16）或可溶性fms样酪氨酸激酶-1（0.7 +/- 0.14）抑制VEGF，减少小管形成和前mmp -2活性（吡哆醛-5-磷酸：0.84 +/- 0.09;Su5416: 0.79 +/- 0.11；或sFlt: 0.88 +/- 0.13）。这种作用被维生素D-3所中和。因此，维生素D-3显著促进体外ecfc血管生成可能是由于VEGF表达和促mmp -2活性的增加。由于血管生成是子痫前期病理生理的一个重要特征，这些发现可以解释维生素D-3在降低子痫前期风险方面的积极作用。
Grundmann M, Haidar M, Placzko S, Niendorf R, Darashchonak N, Hubel CA, von Versen-Hoynck F. Vitamin D improves the angiogenic properties of endothelial progenitor cells. Am J Physiol Cell Physiol 303: C954-C962, 2012. First published August 29, 2012; doi: 10.1152/ajpcell.00030.2012.-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.