Oxysterol enhanced leukocyte-endothelial interaction

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K16202
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TANI Mariko 東京医科歯科大学, 大学院医歯学総合研究科, 寄附研究部門准教授 (90452028)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 酸化コレステロール / 血管炎症

Outline of Final Research Achievements

7-Ketocholesterol is a major dietary cholesterol oxidation product found in high concentrations in atherosclerotic plaques, which contribute to the development of atherosclerosis. 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. 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.

Free Research Field

血管炎症