Non-classical role of vitamin D (WP5133)

Homo sapiens

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).


Humera Fiaz , Susan Coort , Eric Weitz , Egon Willighagen , and Nhung Pham


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Homo sapiens




Pathway Ontology

vitamin D signaling pathway vitamin D metabolic pathway

Disease Ontology

hypertension diabetes mellitus COVID-19


Label Type Compact URI Comment
aldosterone Metabolite wikidata:Q184564
1,25-dihydroxycholecalciferol Metabolite chebi:17823
vitamin D receptor agonists Metabolite chebi:139503
25-hydroxycholecalciferol Metabolite chebi:17933
angiotensin I Metabolite chebi:2718
7-Dehydrocholesterol Metabolite chebi:17759
Cholecalciferol Metabolite chebi:28940
1,25-dihydroxycholecalciferol Metabolite chebi:17823
Angiotensin II Metabolite hmdb:HMDB01035
Angiotensinogen Protein uniprot:P01019
Type-1 angiotensin II receptor Protein uniprot:P30556
Type-2 angiotensin II receptor Protein uniprot:P50052
25-hydroxylase Protein uniprot:E9PS56
Renal Type-1 angiotensin II receptor Protein uniprot:P30556
ACE2 Protein uniprot:Q9BYF1
Renin Protein uniprot:P00797
1-alpha-hydroxylase Protein uniprot:V9GYP0
ACE Protein uniprot:A0A0A0MSN4


  1. Vitamin D and its effects on cardiovascular diseases: a comprehensive review. Pérez-Hernández N, Aptilon-Duque G, Nostroza-Hernández MC, Vargas-Alarcón G, Rodríguez-Pérez JM, Blachman-Braun R. Korean J Intern Med. 2016 Nov;31(6):1018–29. PubMed Europe PMC Scholia
  2. Vitamin D deficiency and diabetes. Berridge MJ. Biochem J. 2017 Mar 24;474(8):1321–32. PubMed Europe PMC Scholia
  3. A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: Implications for a potential treatment for COVID-19. Malek Mahdavi A. Rev Med Virol. 2020 Sep;30(5):e2119. PubMed Europe PMC Scholia
  4. The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms. McLachlan CS. Clin Hypertens. 2020 Jul 15;26:14. PubMed Europe PMC Scholia