Vitamin D promotes vascular regeneration.

Area of Science:

• Cardiovascular biology
• Endocrinology
• Regenerative medicine

Background:

• Vitamin D deficiency is common and linked to inflammation and cardiovascular disease.
• The role of 1,25-dihydroxy-vitamin D3 (1,25-VitD3) in the cardiovascular system is debated, with potential for both harm (calcification) and benefit (anti-inflammatory).
• A hypothesis was formed that 1,25-VitD3 aids vascular repair after injury.

Purpose of the Study:

• To investigate the potential of 1,25-VitD3 in promoting vascular regeneration after injury.
• To elucidate the mechanisms by which 1,25-VitD3 influences vascular healing.

Main Methods:

• Supplementation with vitamin D3 in healthy volunteers and 1,25-VitD3 in mice models of vascular injury (carotid artery, femoral artery ligation).
• Assessment of angiogenic myeloid cells, reendothelialization, and angiogenesis.
• Investigation of the role of CXCR4, SDF1, and hypoxia-inducible factor 1-α (HIF-1α) signaling pathways.
• Utilized conditional knockout models for the vitamin D receptor in specific cell types.

Main Results:

• Vitamin D3 supplementation increased circulating angiogenic myeloid cells in humans.
• 1,25-VitD3 increased angiogenic myeloid cells and promoted reendothelialization in mouse models, including in diabetic mice with impaired angiogenesis.
• The pro-regenerative effects were dependent on SDF1/CXCR4 signaling and vitamin D receptor expression in myeloid cells.
• Mechanistically, 1,25-VitD3 upregulated HIF-1α, which in turn promoted SDF1 expression.

Conclusions:

• Vitamin D3, via 1,25-VitD3, enhances vascular repair and regeneration.
• The mechanism involves the induction of SDF1 by 1,25-VitD3 in myeloid cells, mediated by HIF-1α.
• This highlights vitamin D3 as a potential therapeutic strategy for promoting vascular healing.