Vitamin D-mitochondria cross-talk could modulate the signalling pathway involved in hypertension development: a translational integrative overview

• Published in: Clínica e investigación en arteriosclerosis (Internet, English ed.) English ed.), 2020-07, Vol.32 (4), p.144-155
• Main Authors: Sanz, Raúl, Mazzei, Luciana, Santino, Nicolás, Ingrasia, Marco, Manucha, Walter
• Format: Article
• Language: English
• Subjects: Hipertensión; Hypertension; Mitochondria; Mitocondria; Nitric oxide; Renin-angiotensin-aldosterone system; Sistema renina-angiotensina-aldosterona; Vitamin D; Vitamina D; Óxido nítrico
• ISSN: 2529-9123; 2529-9123
• DOI: 10.1016/j.artere.2020.02.003

Vitamin D deficiency is a worldwide pandemic and results in osteoporosis, hypertension, and other cardiovascular diseases. At the cellular level, it produces significant oxidative stress, inflammatory markers, and mitochondrial damage. There is increasing evidence about the role of vitamin D in the regulation of the renin-angiotensin-aldosterone system (RAAS). Moreover, there is evidence of involvement in cardiovascular complications, as well as in the immune system disorders. Vitamin D values below 25 ng/mL are related to an increase in vascular tone mediated by smooth muscle contraction. Furthermore, it can produce direct effects on vascular smooth muscle cells, RAAS over-regulation, modulation of calcium metabolism, and secondary hyperparathyroidism. All this predisposes patients to develop hypertrophy of the left ventricle and vascular wall, causing hypertension. In this work, a review is presented of the main mechanisms involved in the development of hypertension due to vitamin D deficiency. Among them are the link established between the levels of extra-mitochondrial inorganic phosphate, its main regulatory hormones—such as vitamin D—, the cardiovascular system, reactive oxygen species, and mitochondrial metabolism. The role of the mitochondrial vitamin D receptor and the regulation of the respiratory chain could influence arterial remodelling since its activation would reduce oxidative damage and preserve cell life. However, there are aspects not yet understood about the intricate signalling network that appeared simple in experimental trials, but complex in clinical studies. In this way, the completion of new studies as “VITAL”, could clarify, and thus support or refute the possible benefits of Vitamin D in hypertensive cardiovascular disease. El déficit de vitamina D es una pandemia a nivel mundial y trae como consecuencia osteoporosis, hipertensión arterial (HTA) y otras enfermedades cardiovasculares. A nivel celular produce mayor carga oxidativa, marcadores inflamatorios y daño mitocondrial. Existe cada vez más evidencia sobre el protagonismo de la vitamina D en la regulación del sistema renina-angiotensina-aldosterona (RAAS), con posibles implicancias cardiovasculares así como para el sistema inmunológico. Valores de vitamina D inferiores a 25 ng/mL se relacionan con un aumento de tono vascular mediado por la contracción del músculo liso, ya sea a través de efectos directos sobre las células vasculares del músculo liso, sobrerregulación del RAA