title: Vitamin D receptor deficiency and low vitamin D diet stimulate aortic calcification and osteogenic key factor expression in mice.
abstract: Low levels of 25-hydroxy vitamin D (25(OH)D) are associated with cardiovascular diseases. Herein, we tested the hypothesis that vitamin D deficiency could be a causal factor in atherosclerotic vascular changes and vascular calcification. Aortic root sections of vitamin D receptor knockout (VDR(-/-)) mice that were stained for vascular calcification and immunostained for osteoblastic differentiation factors showed more calcified areas and a higher expression of the osteogenic key factors Msx2, Bmp2, and Runx2 than the wild-type mice (P<0.01). Data from LDL receptor knockout (LDLR(-/-)) mice that were fed western diet with either low (50 IU/kg), recommended (1,000 IU/kg), or high (10,000 IU/kg) amounts of vitamin D(3) over 16 weeks revealed increasing plasma concentrations of 25(OH)D (P<0.001) with increasing intake of vitamin D, whereas levels of calcium and phosphorus in plasma and femur were not influenced by the dietary treatment. Mice treated with the low vitamin D diet had more calcified lesions and a higher expression of Msx2, Bmp2, and Runx2 in aortic roots than mice fed recommended or high amounts of vitamin D (P<0.001). Taken together, these findings indicate vitamin D deficiency as a risk factor for aortic valve and aortic vessel calcification and a stimulator of osteogenic key factor expression in these vascular areas.
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Schmidt
authors.forename: Corinna
authors.initials: C
authors.lastname: Brandsch
authors.forename: Hagen
authors.initials: H
authors.lastname: Kühne
authors.forename: Alexandra
authors.initials: A
authors.lastname: Thiele
authors.forename: Frank
authors.initials: F
authors.lastname: Hirche
authors.forename: Gabriele I
authors.initials: GI
authors.lastname: Stangl
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002114:Calcinosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000097:blood; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004032:Diet; D005269:Femur / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010758:Phosphorus / Q000097:blood / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000473:pathology; D018167:Receptors, Calcitriol / Q000172:deficiency* / Q000235:genetics; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D018398:Homeodomain Proteins; D008055:Lipids; C084119:MSX2 protein; D018167:Receptors, Calcitriol; D011973:Receptors, LDL; C493716:Runx2 protein, mouse; D014807:Vitamin D; D010758:Phosphorus; D002118:Calcium