Elsevier

Kidney International

Volume 69, Issue 8, 2 April 2006, Pages 1377-1384
Kidney International

Original Article
1,25-Dihydroxyvitamin D3 stimulates vascular smooth muscle cell proliferation through a VEGF-mediated pathway

https://doi.org/10.1038/sj.ki.5000304Get rights and content
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Atherosclerosis is a complex process characterized by an increase in the wall thickness owing to the accumulation of cells and extracellular matrix between the endothelium and the smooth muscle cell wall. This process is associated with different pathologies and it is accelerated in patients with chronic renal failure. In these patients, decreased synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) leads to secondary complications, like hyperparathyroidism, and treatment with 1,25(OH)2D3 is a common practice. The effect of 1,25(OH)2D3 on vascular smooth muscle cells (VSMCs) calcification has been widely studied, but the role of 1,25(OH)2D3 on VSMC proliferation remains obscure. We have analyzed the effects of 1,25(OH)2D3 in the proliferation of VSMC. We found that 1,25(OH)2D3 (5–100 nM) induces a dose-dependent increase in VSMC proliferation in quiescent cells and in cells stimulated to grow. This increase in proliferation is achieved by shortening the G1 phase. The effect of 1,25(OH)2D3 on VSMC proliferation is mediated by an increase of the expression of vascular endothelial growth factor A (VEGF), as the inhibition of VEGF activity totally blunted the 1,25(OH)2 D3-induced VSMC proliferation. We found this increase in proliferation in vitro, ex vivo in aortic rings incubated with 1,25(OH)2D3, and in vivo in animals with a model of chronic renal failure (5/6 nephrectomy) treated with 1,25(OH)2D3 (1 μg/kg three times a week for 8 weeks). Thus, we conclude that 1,25(OH)2D3 induces increases in VSMC proliferation through an increase on VEGF expression.

KEYWORDS

calcitriol smooth muscle
proliferation chronic kidney disease

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