Non-classical role of vitamin D

Vitamin D is known for its participation in various skeletal and non-skeletal muscle homeostasis. In addition to Calcium (Ca²⁺) and phosphorous (P) absorption, its association with CVD, hypertention, cancer, obesity, diabetes and immune system has been reported. It actively participates in the regulation of cardiovascular system through Renin Angiotensin Aldosterone System (RAAS). Renin is secreted by the kidney and it activates the formation of angiotensin II that leads to the decreased production of nitric oxide (NO) and increased endothelial vascular dysfunction (Pérez-Hernández et al., 2016). Vitamin D causes the insulin release, facilitates muscle contraction and glucose uptake by enhancing the activity of glucose transporter 4 (GLUT4) channels in the cells (Berridge, 2017) and reduces the aldosterone . From last few years vitamin D has gained special attention as immunomodulatory agent. The immunologic cells such as B cells, T cells, and antigen presenting cells express vitamin D receptors on their cells as well as are capable of synthesizing vitamin D metabolites especially calcitriol. The beneficial effects of vitamin D are linked with both innate and adaptive immune systems. During vitamin D deficiency an unwanted production of pro-inflammatory cytokines cause atherosclerotic lesions and atherogenesis. These conditions lead to increased vasoconstriction and decreased vasodilation, endothelial dysfunction, and alleviated nitric oxide formation. Furthermore, the expression of angiotensin-converting enzyme 2 (ACE2; responsible for the retrospective production of Ang1-7 form Ang II) is also reduced in vitamin D deficient subjects. Such individuals are more vulnerable to infectious diseases, especially, recent pandemic of COVID-19 (Malek Mahdavi, 2020).

维生素D以其在多种骨骼和非骨骼肌肉稳态中的参与而闻名。除了钙（Ca²⁺）和磷（P）的吸收外，其与心血管疾病、高血压、癌症、肥胖、糖尿病和免疫系统关联的报道也屡见不鲜。维生素D通过肾素-血管紧张素-醛固酮系统（RAAS）积极参与心血管系统的调节。肾素由肾脏分泌，它激活了血管紧张素II的形成，导致一氧化氮（NO）的生成减少和内皮血管功能障碍的增加（Pérez-Hernández等，2016）。维生素D可促进胰岛素释放，通过增强细胞中葡萄糖转运蛋白4（GLUT4）通道的活性，促进肌肉收缩和葡萄糖摄取，并降低醛固酮水平（Berridge，2017）。在过去的几年中，维生素D作为免疫调节剂受到了特别的关注。免疫细胞，如B细胞、T细胞和抗原呈递细胞，在其细胞上表达维生素D受体，并能够合成维生素D代谢物，尤其是钙三醇。维生素D的有益作用与先天性和适应性免疫系统相关。在维生素D缺乏的情况下，促炎细胞因子的过度产生会导致动脉粥样硬化性病变和动脉粥样硬化。这些条件会导致血管收缩增加、血管舒张减少、内皮功能障碍以及一氧化氮生成减少。此外，维生素D缺乏者中血管紧张素转化酶2（ACE2；负责从血管紧张素II逆向产生Ang1-7形式）的表达也降低。这类个体更容易受到感染性疾病的影响，尤其是最近的COVID-19大流行（Malek Mahdavi，2020）。