Molecular mechanism of vitamin D in the cardiovascular system

Abstract

Vitamin D deficiency is a global health problem that has various adverse consequences. Vitamin D is mainly synthesized in the skin by sunlight (UV light) irradiation; therefore, vitamin D status is influenced by geographic locations, seasonal changes, and skin pigmentations. The kidney is involved in the biosynthesis of 1,25-dihydroxyvitamin D and the reuptake of filtered 25-hydroxyvitamin D from the proximal tubules, thus, vitamin D deficiency is highly prevalent in patients with kidney disease who have renal insufficiency. There is a growing body of epidemiological and clinical evidence in the literature that links vitamin D deficiency to cardiovascular disease. The discovery of the vitamin D hormone functioning as an endocrine inhibitor of the renin-angiotensin system provides an explanation for this association. This review will discuss the mechanism underlying the connection between vitamin D and cardiovascular disease and its physiological and therapeutic implications.

Figure 1

Vitamin D analogs block the compensatory induction of renin in combination therapy. The homeostasis of renin production is maintained by the negative feedback loop mediated by AT1 receptor. Inhibition of the RAS by the three classes of inhibitors (renin inhibitors, ACE inhibitors and ARB) disrupts the feedback loop leading to increased renin production. Ultimately Ang II levels can be raised, which reduces reduced the efficacy of the drugs. In combination therapy, vitamin D analogs are able to block the compensatory increase of renin by suppressing renin gene expression, and that improves the therapeutic efficacy.