Calcitriol prevents inflammatory gene expression in macrovascular endothelial cells.

BACKGROUND: Calcitriol (vitamin D) supplementation has been proposed for therapeutical use in vascular diseases due to its immunomodulatory activity, preventing inflammation and promoting angiogenesis. In the present study, we hypothesised whether calcitriol downregulates pro-inflammatory gene expression without affecting angiogenesis and anti-inflammatory gene expression in LPS-induced endothelial cells. METHOD: In order to evaluate the effect of calcitriol in suppressing inflammatory gene expression in the endothelium, endothelial cells were exposed to the physiological concentration of calcitriol followed by stimulation with lipopolysaccharide (LPS). Gene expression of interleukin (IL)-1ß, Transforming Growth Factor (TGF)-ß, Human ß-defensin (HBD)-2, angiogenin (ANG) and cathelicidin (LL-37) were quantified by quantitative polymerase chain reaction. RESULTS: The results from six independent experiments conducted in duplicate, showed that calcitriol decreased IL-1ß (p < 0.01) and HBD-2 expression (p < 0.01) when compared to non-treated cells. However, calcitriol treatment had no effect on TGF-ß, ANG and LL-37 gene expression. CONCLUSION: Calcitriol prevents inflammatory gene expression, but does not affect expression of angiogenic genes in endothelial cells, which suggest the potential use of calcitriol to prevent endothelial activation through the downregulation of IL-1ß and HBD-2.

Coronary flow-induced inotropism is modulated by binding of dextrans to the endothelial luminal surface.

In isolated perfused guinea pig hearts, coronary flow causes a positive inotropic effect [positive coronary flow-induced effect (+CFIE)] that could be altered by dextrans (Dx) in the coronary perfusion solution. To test this possibility, Dx of 20, 40, 70, and 500 kDa were infused and found to modulate +CFIE; however, when Dx infusion was terminated, the effect persisted, i.e., was irreversible/nonwashable, suggesting that Dx may bind to luminal endothelial lectinic structures. This hypothesis was tested when Dx [with fluorescent traces (D*)] bound to the vessel wall was hydrolyzed by dextranase infusion and washout of D* fragments completely reverted the +CFIE, and it was found that bound D* to be displaced by free Dx required concentrations 50-100 times that used during binding. In addition, dose-response curves for Dx on +CFIE show that the higher the Dx molecular mass, the lesser the concentration required to have an effect. Because a large Dx molecule has a greater number polymeric glucose branches, it can bind to a larger number of endothelial lectinic sites, requiring a lower concentration to affect +CFIE. Our results suggest that luminal endothelial lectinic structures are part of the flow-sensing assembly.