Vitamin D and regulation of vascular cell function.

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)2D3] 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)2D3 and VDR in the regulation of perivascular supporting cell function. In addition, the interaction of 1,25(OH)2D3 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)2D3 regulation in vascular cells will allow us to identify novel pathways that are targets for regulation of vascular function and angiogenesis.