1,25-dihydroxyvitamin D3 receptor is upregulated in aortic smooth muscle cells during hypervitaminosis D.
Several studies have demonstrated that excess of vitamin D3 is toxic particularly to vascular tissues. A notable pathological feature is arterial calcification. The nature of the toxic metabolite in hypervitaminosis D and the pathogenesis of arterial calcification are not clearly understood. The present study was undertaken to explore whether arterial calcification is a sequel of increased calcium uptake by arterial smooth muscle mediated by up regulation of vitamin D receptor in the cells in response to elevated circulating levels of vitamin D3 in serum. The experimental study was performed in 20 New Zealand white female rabbits aged 6 months. Animals in the test group were injected 10,000 IU of cholecalciferol intramuscularly twice a week for one month. Six control animals were given intra-muscular injections of plain cottonseed oil. Animals were sacrificed and aortas were examined for pathological lesions, 1,25-dihyroxyvitamin D3 (1,25(OH)2 D3) receptor levels and 45Ca uptake in smooth muscle cells. Serum samples collected at intervals were assayed for levels of 25-OH-D3 and calcium. The results showed that in animals given injections of cholecalciferol, serum levels of 25-OH-D3 were elevated. In four of these animals calcification and aneurysmal changes were seen in the aorta. Histological lesions comprised of fragmentation of elastic fibers as well as extensive loss of elastic layers. 1,25(OH)2 D3 receptor levels were up regulated and 45Ca uptake enhanced in aortas of animals which were given excessive vitamin D3. The evidences gathered suggest that excess vitamin D is arteriotoxic and that the vitamin induces arterial calcification through up regulation of 1,25(OH)2D3 receptor and increased calcium uptake in smooth muscle cells of the arteries.
Rajasree
S
S
Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
Umashankar
P R
PR
Lal
A V
AV
Sarma
P Sankara
PS
Kartha
C C
CC
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D002112:Calcifediol / Q000097:blood; D002114:Calcinosis / Q000209:etiology / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007273:Injections, Intramuscular; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D011817:Rabbits; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015854:Up-Regulation
D018167:Receptors, Calcitriol; D002762:Cholecalciferol; D002112:Calcifediol; D002118:Calcium