7-Ketocholesterol enhances leukocyte adhesion to endothelial cells via p38MAPK pathway

• Published in: PloS one Vol. 13; no. 7; p. e0200499
• Main Authors: Tani, Mariko, Kamata, Yuko, Deushi, Michiyo, Osaka, Mizuko, Yoshida, Masayuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.07.2018; Public Library of Science (PLoS)
• Subjects: Activating transcription factor 2; Adhesion; Arteriosclerosis; Atherosclerosis; Bioethics; Biology and Life Sciences; Cardiovascular disease; Cell adhesion; Cell adhesion & migration; Cholesterol; Coronary vessels; Diet; E-selectin; Endothelial cells; Endothelium; Experiments; Health aspects; Inflammation; Intercellular adhesion molecule 1; Kinases; Leukocytes; Life sciences; MAP kinase; Medicine and Health Sciences; Monocytes; Oxidation; p38 mitogen-activated protein kinases; Penicillin; Plaques; Pretreatment; Protein kinase; Proteins; Transcription factors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Umbilical vein; Vascular cell adhesion molecule 1; Vascular endothelial growth factor; White blood cells; United States > US; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0200499

7-Ketocholesterol is a major dietary cholesterol oxidation product found in high concentrations in atherosclerotic plaques, which contribute to the development of atherosclerosis. This study aimed to investigate the effects of 7-ketocholesterol on endothelial inflammation, as well as the underlying mechanisms. Pretreatment of human umbilical vein endothelial cells (HUVEC) with 7-ketocholesterol significantly enhanced the total interactions between human monocytic cells (THP-1 cell line) and TNFα-activated HUVECs under physiological flow conditions, compared to pretreatment with cholesterol (TNFα+50 μM cholesterol: 13.1 ± 0.54 cells/CPF, TNFα+50 μM 7-ketocholesterol: 18.9 ± 0.35 cells/CPF, p < 0.01). 7-Ketocholesterol enhanced the expression of E-selectin, ICAM-1, and VCAM-1 proteins. It also activated p38 mitogen-activated protein kinase (MAPK), and treatment with a p38 MAPK inhibitor inhibited both E-selectin expression via ATF-2 activation and 7-ketocholesterol-induced THP-1 adhesion to HUVECs. These findings suggest that 7-ketocholesterol enhances leukocyte-endothelial interactions by upregulating the expression of adhesion molecules, presumably via the p38 MAPK-dependent pathway.