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).
Authors
Humera Fiaz , Susan Coort , Eric Weitz , Egon Willighagen , and Nhung PhamActivity
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Organisms
Homo sapiensCommunities
COVID-19Annotations
Pathway Ontology
vitamin D signaling pathway vitamin D metabolic pathwayDisease Ontology
hypertension diabetes mellitus COVID-19Label | 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 | |
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 |
References
- 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
- Vitamin D deficiency and diabetes. Berridge MJ. Biochem J. 2017 Mar 24;474(8):1321–32. PubMed Europe PMC Scholia
- 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
- 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