Endocrine Abstracts

Vitamin D has been shown not only to be important for bone and calcium metabolism but also for homeostasis of critical tissues involved in vascular disease. The vitamin D receptor (VDR) and the 1a-hydroxylase enzyme are present in critical cells implicated in the development of vascular disease. Vitamin D influences multiple mechanisms to decrease vascular inflammation: it suppresses the renin-angiotensin system, promotes endothelial nitric oxide release, decreases vascular inflammatory markers and cholesterol deposition, and imbues immune cells with anti-inflammatory properties. Studies in our mouse models of diet-induced insulin resistance show that vitamin D deficiency or conditional deletion of VDR in macrophages promotes insulin resistance, renin-dependent hypertension, and accelerates atherosclerosis. In type 2 diabetes patients, vitamin D deficiency promotes a pro-inflammatory monocyte phenotype with increased adhesion and migration to endothelial cells. Conversely, 25(OH)D or 1,25(OH)2D3 supplementation in culture suppresses this pro-inflammatory monocyte phenotype and reduces cellular cholesterol content by downregulation of ER stress, suggesting that reduced monocyte vitamin D signaling is a critical mechanism for vascular invasion and atherosclerosis. Human observational studies indicate consistent associations between low 25(OH)D levels and increased cardiovascular disease, but the effects of vitamin D supplementation for prevention are conflicting, and study design limitations preclude adequate conclusions.