title: Paricalcitol attenuates lipopolysaccharide-induced myocardial inflammation by regulating the NF-κB signaling pathway.
abstract: 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 inflammation and fibrosis. In the present study, we aimed to investigate the effects of paricalcitol on lipopolysaccharide (LPS)-induced myocardial inflammation and 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 induce endothelial cell inflammation. For in vivo experiments, myocardial inflammation was induced by an intraperitoneal injection of 15 mg/kg LPS into C57BL6 mice pre-treated with or without 0.2 µg/kg paricalcitol. Treatment with paricalcitol suppressed the TNF-α-induced increase 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 paricalcitol also decreased the TNF-α-induced nuclear factor (NF)-κB binding activity. In a mouse model of LPS-induced myocardial inflammation, pre-treatment with paricalcitol prevented the LPS-induced increase in the expression of myocardial ICAM-1, phosphorylated p65 and myocardial TNF-α. Pre-treatment with paricalcitol also alleviated endotoxemia‑induced microvascular leakage in the myocardium. The findings of our study suggest that paricalcitol exerts a protective effect against LPS-induced myocardial inflammation by regulating the expression of cell adhesion molecules and TNF-α, and by improving myocardial permeability.
authors.affiliation: Division of Functional Food Research, Korea Food Research Institute, Seongnam-si, Gyeonggi-do 13539, Republic of Korea.
authors.forename: Ae Sin
authors.initials: AS
authors.lastname: Lee
authors.affiliation: Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju-si, Jeollabuk‑do 54907, Republic of Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju-si, Jeollabuk‑do 54907, Republic of Korea.
authors.forename: Tùng Nguyễn
authors.initials: TN
authors.lastname: Thanh
authors.affiliation: Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju-si, Jeollabuk‑do 54907, Republic of Korea.
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.affiliation: Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju-si, Jeollabuk‑do 54907, Republic of Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.affiliation: Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju-si, Jeollabuk‑do 54907, Republic of Korea.
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.affiliation: Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju-si, Jeollabuk‑do 54907, Republic of Korea.
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D004872:Ergocalciferols / Q000494:pharmacology / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C084656:paricalcitol