IJCS | Volume 31, Nº4, July / August 2018

424 Jorge et al. Vitamin D and cardiovascular disease Int J Cardiovasc Sci. 2018;31(4)422-432 Review Article D-binding protein (VDBP), 10 to 15% to albumin, and the remaining (less than 1%) circulate in a free form. There are fewdata in the literature on the bioavailability of vitamin D bound to albumin; therefore, the expression “vitamin D bioavailability” is used for the 25- hydroxyvitamin D form not bound to VDBP. 12 When reaching target tissues, 25-hydroxyvitamin D is converted by the enzyme 1 α -hydroxylase into 1 α ,25- dihydroxyvitamin D, which is the metabolically active form of the vitamin. The effects of 1 α ,25-dihydroxyvitaminD aremediated by its receptor, VDR, which belongs to the family of nuclear receptors 1. Both the enzyme 1 α -hydroxylase and the VDR receptor are found in almost all human cells, including cardiomyocytes 13 and vascular smooth muscle cells. 14 Experimental models with absence of VDR allow the understanding of the tissue-specific activity of the receptor. As an example, the absence of VDR results in increased ventricular mass, increased brain natriuretic peptide (BNP) levels and deregulation of cardiac metalloproteinases and fibroblasts, promoting a fibrotic extracellular matrix and leading to ventricular dilation and electromechanical uncoupling. 15 After the binding of vitamin D to the VDR, the complex promotes gene activation or suppression, with the help of coregulator proteins. On the other hand, the VDR also presents prompt nongenomic responses by inducing voltage-dependent calcium channels, leading to increased cell inflow of calcium and activation of other messengers, such as cyclic AMP, protein kinase A, and phospholipase C. 16 Vitamin D deficiency The American guideline for evaluation, prevention, and treatment of vitamin D deficiency 17 establishes that the body pool of the vitamin should be determined by measurement of serum 25-hydroxyvitamin D with the following cutoff points: (i) deficiency, when below or equal to 20 ng/mL, (ii) insufficiency, when between 20 and 30 ng/mL, and (iii) sufficiency when greater than 30 ng/mL. Some risk factors for vitamin D deficiency have been observed and relate to sun exposure, dietary habits, and intestinal absorption. These include an indoor lifestyle (sun deprivation), use of sunscreens, advanced age, distance from the Equator, black skin, air pollution, smoking, poor food absorption (malabsorption syndromes), drugs (anticonvulsants, glucocorticoids), and kidney and liver disease. 10,17 Figure 2 - Vitamin D2 and D3 molecules, showing the difference in methyl group (CH3), which is present in the former and absent in the later (arrows). Extracted from: Peixoto PV et al. Hypervitaminosis D in animals [Hipervitaminose D em animais]. Pesq. Vet. Bras. 32(7):573-594, julho 2012. vitamin D2 vitamin D3