Paricalcitol attenuates lipopolysaccharide-induced myocardial inflammation by regulating the NF-κB signaling pathway.

Vitamin D deficiency is associated with an increased risk of cardiovascular disease, diabetes, colon and breast cancer, infectious diseases and allergies. Vascular alterations are an important pathophysiological mechanism of sepsis. Experimental data suggest that paricalcitol, a vitamin D2 analogue, exerts beneficial effects on renal inflammationand fibrosis. In the present study, we aimed to investigate the effects of paricalcitolon lipopolysaccharide (LPS)- inducedmyocardial inflammationand to elucidate the underlying mechanisms. We used primary cultured human umbilical vein endothelial cells for in vitro experiments, in which stimulation with tumor necrosis factor (TNF)-α was used to induceendothelial cell inflammation. For in vivo experiments, myocardial inflammationwas inducedby an intraperitoneal injection of 15 mg/kg LPS into C57BL6 mice pre-treated with or without 0.2 µg/kg paricalcitol. Treatment with paricalcitolsuppressed the TNF-α- inducedincrease in the protein expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 ( VCAM-1) and fractalkine in endothelial cells. Treatment with paricalcitolalso decreased the TNF-α- inducednuclear factor (NF)-κB binding activity. In a mouse model of LPS- inducedmyocardial inflammation, pre-treatment with paricalcitolprevented the LPS- inducedincrease in the expression of myocardial ICAM-1, phosphorylated p65 and myocardial TNF-α. Pre-treatment with paricalcitolalso alleviated endotoxemia- inducedmicrovascular leakage in the myocardium. The findings of our study suggest that paricalcitolexerts a protective effect against LPS- inducedmyocardial inflammationby regulating the expression of cell adhesion moleculesand TNF-α, and by improving myocardial permeability.