Diabetes is associated with vascular dysfunction, attenuated vascular regeneration and reduced numbers of EPCs. Diabetes has been linked to low function of activate vitamin D3 (1,25 Dihydroxycholecalciferol, VitD) and VitD is through to have anti-inflammatory properties. We hypothesize that supplementation of activate VitD3 restores vascular function and regeneration in diabetic mice.

Diabetes was induced by streptozotocin treatment and vascular regeneration was study after carotid artery electric injury. VitD (100ng/kg/d 3, consecutive days i.p.) improved acetylcholine-induced endothelium-dependent vasodilatation and increased nitric oxide availability in C57Bl/6 mice, without affecting eNOS expression or vascular radical production. Rather, VitD increased the number of endothelial progenitor cells (EPCs; CD45-, CD117+, CD34+) in blood and bone marrow and this was accompanied by enhanced endothelial regeneration of the injured carotid artery. Importantly, in diabetic mice, VitD restored the attenuated vascular healing to the same level as healthy mice treated with VitD. VitD also restored the number colony forming units from the spleen as an indicator of tissue repair capacity. As an underlying mechanism we identified SDF-1 alpha and CXCR4 to be increased in injured vessels and to be further increased after vitamin D3 treatment. Blocking CXCR4 by AMD3100 (1,25mg/kg/d) abrogated the positive effect of vitamin D3 on vascular healing.

Our data indicate that vitamin D3 improves vascular healing via stimulation of the SDF-1 alpha axis and eventually tissue repair capacity in healthy as well as in diabetic mice.