The effect of vitamin D derivatives on vascular calcification associated with inflammation

Background. Vitamin D sterols may modulate vascular response to inflammation and vascular calcification (VC). Methods. Rat aortic rings (RARs) and human vascular smooth muscle cells (HVSMCs) were treated in vitro with phosphate (P), tumour necrosis factor alpha (TNF-alpha), calcitriol (CTR) and paricalcitol (PCT). Rats having undergone subtotal nephrectomy (Nx) (n = 66) on a high-phosphorus diet were treated with Escherichia coli lipopolysacharide (LPS) (40-400 mu g/kg/day) or LPS plus CTR (80 ng/kg/48 h) or LPS plus PCT (240 ng/kg/48 h) for 14 days. Results. In vitro, the addition of TNF-alpha to the medium increased the mineral content of RAR and HVSMC. Treatment with both vitamin D analogues decreased bone morphogenetic protein 2 but did not modify Runx-2. Calcification was prevented only by PCT. In vivo, treatment with LPS increased plasma levels of TNF-alpha, monocyte chemotactic protein-1 and interleukin-1alfa and induced calcification. The concomitant administration of LPS with either CTR or PCT led to a significant decrease in cytokine plasma levels and the decrease was more accentuated after treatment with PCT than with CTR. Rats treated with CTR showed an elevation in aortic Ca and marked Von Kossa staining; however, rats treated with PCT did not increase aortic Ca and did not show Von Kossa staining. Conclusion. Treatment with PCT resulted in more marked anti-inflammatory effect than treatment with CTR and, as opposed to CTR, PCT prevented VC.