Are vitamin D receptor activators useful for the treatment of thrombosis?

Vitamin D3 is produced in the skin and modified in the liver and kidneys to form the active metabolite 1,25-dihydroxyvitamin D3 (calcitriol). Calcitriol binds to the vitamin D receptor (VDR), a nuclear receptor. The binding of calcitriol to the VDR activates the recruitment of cofactors that form a transcriptional complex that binds vitamin D response elements in the promoter region of target genes. During the past three decades, VDR research has focused mainly on the role of the receptor in the regulation of parathyroid hormone, intestinal calcium and phosphate absorption, and bone metabolism, and several VDR activators have been developed for the treatment of osteoporosis, psoriasis and hyperparathyroidism secondary to chronic kidney diseases. Emerging evidence suggests that VDR activators may be useful for treating cardiovascular, immunological, inflammatory and renal diseases. In addition, the VDR may have a role in modulating thrombogenicity. For example, VDR-/- mice display a phenotype of increased thrombogenic activity. VDR activators modulate the expression of various factors involved in thrombogenicity. Calcitriol was demonstrated to reduce the rate of oncology-related thrombosis in a clinical trial. This review discusses evidence from preclinical and clinical studies to investigate the potential role of VDR in thrombogenicity, and assesses whether VDR activators can be useful in the treatment of thrombosis.