Title:Vitamin D and Vitamin D Receptor Activators in Treatment of Hypertension and Cardiovascular Disease
Volume: 14
Issue: 1
Author(s): Agata Franczyk, Katarzyna Stolarz-Skrzypek, Anna Wesołowska and Danuta Czarnecka
Affiliation:
Keywords:
Vitamin D, cardiovascular system, vitamin D receptor activators, vitamin D supplementation, hypertension,
vitamin D receptor, vitamin D analogues.
Abstract: Vitamin D plays an essential role in calcium homeostasis and bone metabolism, but recent research has
exposed a larger spectrum of biological actions that also includes induction of cell proliferation, immunomodulation, and
control of other hormonal systems. Many cells that play an important role in the cardiovascular system express the
Vitamin D receptor (VDR) and respond to 1,25-(OH)2D (the active product of vitamin D conversion by hydroxylase) with
cell-specific function and gene regulation. These cells include cardiomyocytes, vascular endothelial cells, vascular smooth
muscle cells, phagocytes, and cells of the nephron, which produce renin.
VDR activators (calcitriol and paricalcitol) are available for the treatment of vitamin D deficiency, which can result from
inadequate cutaneous production and/or low dietary intake. Vitamin-D deficient patients present a higher risk of
cardiovascular disease than the general population. Recent clinical observations have shown that VDR activator therapy
provides survival benefit and also has a positive impact on cardiovascular function.
Compelling results have arisen from previous studies of mice with disrupted genes of the vitamin D signaling pathways.
In mice lacking VDR or CYP27B1 (1α-hydroxylase – an enzyme, which converts vitamin D to its active form), in
addition to the expected phenotype (hypocalcaemia, secondary hyperparathyroidism and osteomalacia), development of
hypertension and cardiac hypertrophy were also observed. Moreover, these mice presented with overexpression of renin
and atrial natriuretic peptide.
VDR may play a role in regulating smooth-muscle-cell (SMC) proliferation, thrombosis, fibrinolysis and vessel
relaxation. The influence of VDR activators on the modulation of renin expression and vascular function may reduce
mortality, organ damage, and cardiovascular morbidity in VDR-activator-treated patients with hypertension.
Since clinical use of calcitriol is largely limited, because of the side effect of hypercalcemia, calcitriol analogues have
been synthesized to obtain compounds with better therapeutic profiles.
The main purpose of this article is to review the role of vitamin D and vitamin D receptor activators in cardiovascular
diseases, especially hypertension and its treatment. Due to the high prevalence of hypovitaminosis D among patients with
high cardiovascular risk, vitamin D supplementation therapy may be warranted in this population.