Vitamin D Promotes Vascular Regeneration
| Autor: | Stefan Offermanns, Bernhard Brüne, Christoph Schürmann, Geert Carmeliet, Eva Herrmann, Dieter Steinhilber, Andreas Weigert, Nathalie Dehne, Christoph Kruse, Ajay M. Shah, Matthias S. Leisegang, Ralf P. Brandes, Klaus Badenhoop, Juri Vogel, Katrin Schröder, Michael Sze Ka Wong |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Vitamin Receptors CXCR4 medicine.medical_specialty Endothelium Angiogenesis Neovascularization Physiologic Inflammation Mice chemistry.chemical_compound Calcitriol Physiology (medical) Internal medicine medicine Vitamin D and neurology Animals Humans Regeneration Myeloid Cells business.industry Regeneration (biology) Hypoxia-Inducible Factor 1 alpha Subunit Chemokine CXCL12 medicine.anatomical_structure Endocrinology chemistry Female Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine business Cholecalciferol Hormone |
| Zdroj: | Circulation. 130:976-986 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Background— Vitamin D deficiency in humans is frequent and has been associated with inflammation. The role of the active hormone 1,25-dihydroxycholecalciferol (1,25-dihydroxy-vitamin D 3 ; 1,25-VitD3) in the cardiovascular system is controversial. High doses induce vascular calcification; vitamin D 3 deficiency, however, has been linked to cardiovascular disease because the hormone has anti-inflammatory properties. We therefore hypothesized that 1,25-VitD3 promotes regeneration after vascular injury. Methods and Results— In healthy volunteers, supplementation of vitamin D 3 (4000 IU cholecalciferol per day) increased the number of circulating CD45-CD117+Sca1+Flk1+ angiogenic myeloid cells, which are thought to promote vascular regeneration. Similarly, in mice, 1,25-VitD3 (100 ng/kg per day) increased the number of angiogenic myeloid cells and promoted reendothelialization in the carotid artery injury model. In streptozotocin-induced diabetic mice, 1,25-VitD3 also promoted reendothelialization and restored the impaired angiogenesis in the femoral artery ligation model. Angiogenic myeloid cells home through the stromal cell–derived factor 1 (SDF1) receptor CXCR4. Inhibition of CXCR4 blocked 1,25-VitD3–stimulated healing, pointing to a role of SDF1. The combination of injury and 1,25-VitD3 increased SDF1 in vessels. Conditioned medium from injured, 1,25-VitD3–treated arteries elicited a chemotactic effect on angiogenic myeloid cells, which was blocked by SDF1-neutralizing antibodies. Conditional knockout of the vitamin D receptor in myeloid cells but not the endothelium or smooth muscle cells blocked the effects of 1,25-VitD3 on healing and prevented SDF1 formation. Mechanistically, 1,25-VitD3 increased hypoxia-inducible factor 1-α through binding to its promoter. Increased hypoxia-inducible factor signaling subsequently promoted SDF1 expression, as revealed by reporter assays and knockout and inhibitory strategies of hypoxia-inducible factor 1-α. Conclusions— By inducing SDF1, vitamin D 3 is a novel approach to promote vascular repair. |
| Databáze: | OpenAIRE |
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