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 Pham

Activity

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Organisms

Homo sapiens

Communities

COVID-19 ONTOX

Annotations

Pathway Ontology

vitamin D metabolic pathway vitamin D signaling pathway

Disease Ontology

diabetes mellitus COVID-19 hypertension

Participants

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
Angiotensin II Metabolite hmdb:HMDB01035
AGT Protein uniprot:P01019 'Angiotensinogen' originally
AGTR1 Protein uniprot:P30556 'Type-1 angiotensin II receptor' originally
AGTR2 Protein uniprot:P50052 'Type-2 angiotensin II receptor' originally
CYP2R1 Protein uniprot:E9PS56 '25-hydroxylase' originally
AGTR1 Protein uniprot:P30556 'Renal Type-1 angiotensin II receptor' originally
ACE2 Protein uniprot:Q9BYF1
REN Protein uniprot:P00797 'Renin' originally
CYP27B1 Protein uniprot:V9GYP0 '1-alpha-hydroxylase' originally
ACE Protein uniprot:A0A0A0MSN4

References

  1. 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