7-Ketocholesterol enhances leukocyte adhesion to endothelial cells via p38MAPK pathway.
Mariko TaniYuko KamataMichiyo DeushiMizuko OsakaMasayuki YoshidaPublished in: PloS one (2018)
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.
Keyphrases
- oxidative stress
- induced apoptosis
- endothelial cells
- high glucose
- poor prognosis
- rheumatoid arthritis
- cell cycle arrest
- cardiovascular disease
- binding protein
- signaling pathway
- peripheral blood
- long non coding rna
- nitric oxide
- cell death
- genome editing
- pseudomonas aeruginosa
- tyrosine kinase
- cell adhesion
- cell proliferation
- combination therapy
- replacement therapy