title: Dietary vitamin D inadequacy accelerates calcification and osteoblast-like cell formation in the vascular system of LDL receptor knockout and wild-type mice.
abstract: Vitamin D insufficiency is highly associated with cardiovascular morbidity and mortality. We have demonstrated enhanced vascular calcification in LDL receptor knockout (LDLR(-/-)) mice fed a diet low in vitamin D. This study aimed to investigate the impact of a diet low in vitamin D on vascular calcification in wild-type (WT) mice lacking atherosclerotic plaques and the effects of a persistent and discontinuous vitamin D insufficiency on atherosclerotic plaque composition in LDLR(-/-) mice. The study was performed with 4-wk-old male WT and LDLR(-/-) mice that were fed a normal calcium/phosphate Western diet (210 g/kg fat, 1.5 g/kg cholesterol) containing either adequate (+D; 1000 IU/kg) or low (-D; 50 IU/kg) amounts of vitamin D-3 for 16 wk. Four groups of LDLR(-/-) mice received 1 of the 2 diets for additional 16 wk (total 32 wk) and were compared with mice fed the diets for only 16 wk. WT and LDLR(-/-) mice that were fed the -D diet for 16 wk tended to develop more calcified spots in the aortic valve than mice fed the +D diet (+50% and +56%, respectively; P < 0.10). In LDLR(-/-) mice, the extent of calcification increased from week 16 to week 32 and was higher in the -D than in the +D group (P < 0.05). The calcification, owing to the -D diet, was accompanied by highly expressed osteoblast differentiation factors, indicating a transdifferentiation of vascular cells to osteoblast-like cells. Feeding the +D diet subsequent to the -D diet reduced the vascular calcification (P < 0.05). LDLR(-/-) mice fed the -D diet for 32 wk had higher plaque lipid depositions (+48%, P < 0.05) and a higher expression of cluster of differentiation 68 (+31%, P < 0.05) and tumor necrosis factor α (+134%, P < 0.001) than the +D group. Collectively, the findings imply low vitamin D status as a causal factor for vascular calcification and atherosclerosis.
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: Alexandra
authors.initials: A
authors.lastname: Schutkowski
authors.forename: Frank
authors.initials: F
authors.lastname: Hirche
authors.forename: Gabriele I
authors.initials: GI
authors.lastname: Stangl
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000097:blood; D000821:Animal Feed; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000097:blood; D005838:Genotype; D008297:Male; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010710:Phosphates / Q000097:blood; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D061205:Vascular Calcification / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014807:Vitamin D / Q000097:blood* / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014815:Vitamins / Q000097:blood / Q000494:pharmacology
chemical_list: D010710:Phosphates; D011973:Receptors, LDL; D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol; D002118:Calcium