Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin.
McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin.
Am J Physiol Heart Circ Physiol. 2018 Apr 1;314(4):H753-H765. doi: 10.1152/ajpheart.00319.2017. Epub 2017 Dec 22.
Vitamin D deficiency is linked to pathogenesis of many diseases including cardiovascular, cancer, and various eye diseases. In recent years, important roles for vitamin D in regulation of immune function, inflammation, angiogenesis, and aging have been demonstrated. Thus, vitamin D and its analogs have been evaluated for the treatment of various types of cancer and chronic diseases. We have previously shown that the active form of vitamin D [1,25(OH)D] is a potent inhibitor of angiogenesis. This activity is consistent with the important role proposed for vitamin D and its analogs in the mitigation of tumor growth through inhibition of angiogenesis. Here, we review the important nutritional value of vitamin D and the abnormalities linked to its deficiency. We will explore its potential role as a regulator of angiogenesis and vascular cell function and the role vitamin D receptor (VDR) expression plays in these activities during vascular development and neovascularization. Our studies have established an important role for 1,25(OH)D and VDR in the regulation of perivascular supporting cell function. In addition, the interaction of 1,25(OH)D and VDR is essential for these activities and inhibition of neovascularization. Delineating the signaling pathways involved and identification of genes that are the target of 1,25(OH)D regulation in vascular cells will allow us to identify novel pathways that are targets for regulation of vascular function and angiogenesis.
维生素 D 缺乏与许多疾病的发病机制有关,包括心血管疾病、癌症和各种眼病。近年来,已经证明维生素 D 在调节免疫功能、炎症、血管生成和衰老方面具有重要作用。因此,维生素 D 及其类似物已被评估用于治疗各种类型的癌症和慢性疾病。我们之前已经表明,维生素 D 的活性形式[1,25(OH)D]是一种有效的血管生成抑制剂。这种活性与维生素 D 及其类似物通过抑制血管生成来减轻肿瘤生长的重要作用一致。在这里,我们回顾了维生素 D 的重要营养价值及其与缺乏相关的异常。我们将探讨其作为血管生成和血管细胞功能调节剂的潜在作用,以及维生素 D 受体 (VDR) 表达在血管发育和新血管形成过程中这些活性中的作用。我们的研究已经确立了 1,25(OH)D 和 VDR 在调节血管周围支持细胞功能中的重要作用。此外,1,25(OH)D 和 VDR 的相互作用对于这些活动和抑制新血管形成是必不可少的。阐明涉及的信号通路以及确定血管细胞中 1,25(OH)D 调节的靶基因将使我们能够识别血管功能和血管生成调节的新靶点。