From the Second Department of Internal Medicine, Osaka City University
Medical School, Osaka 545, Japan.
Correspondence to Atsushi Shioi, MD, Second Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545, Japan. E-mail as{at}msic.med.osaka-cu.ac.jp
Background—A significant
association between vascular calcification and osteoporosis has been
noted, suggesting that calcium homeostasis is important in vascular
calcification as well as in osteoporosis. Moreover, results of our
previous studies suggest that calcium-regulating hormones such as
parathyroid hormone–related peptide (PTHrP) may modulate vascular
calcification. Therefore, we hypothesized that 1
Methods and Results—We investigated the effect of
1,25(OH)2D3 on in vitro calcification by bovine
vascular smooth muscle cells (BVSMCs).
1,25(OH)2D3 dose dependently increased BVSMC
calcification and alkaline phosphatase activity.
1,25(OH)2D3 also decreased secretion of PTHrP
by BVSMCs in a dose-dependent manner and depressed its gene expression.
Furthermore, exogenous PTHrP (fragment 1-34) antagonized the
stimulatory effect of 1,25(OH)2D3 on BVSMCs.
Finally, 1,25(OH)2D3 dose dependently increased
the expression of the osteopontin gene, one of the bone matrix proteins
in BVSMCs, contributing to its stimulatory action on BVSMC
calcification.
Conclusions—These data suggest that
1,25(OH)2D3 exerts a stimulatory effect on
vascular calcification through direct inhibition of the expression of
PTHrP in BVSMCs as an endogenous
inhibitor of vascular calcification. Moreover, the
stimulatory effects of 1,25(OH)2D3 on alkaline
phosphatase activity and osteopontin expression may contribute to its
promoting action in vascular calcification.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
1,25-Dihydroxyvitamin D3 Increases In Vitro Vascular Calcification by Modulating Secretion of Endogenous Parathyroid Hormone–Related Peptide
,25-dihydroxyvitamin
D3 [1,25(OH)2D3] may have a
direct impact on the calcium-regulating system of vascular smooth
muscle cells, resulting in deposition of calcium in vascular
wall.
Key Words: calcification • vitamin D • muscle, smooth • peptides • osteoporosis
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