15-oxoeicosatetraenoic acid mediates monocyte adhesion to endothelial cell

Lipids in Health and Disease

Research

Buxing Chen¹  Sufen Ren¹  Caixia Guo¹  Guohua Ma²  Yansong Guo³  Lixin Wei⁴  Lemin Zheng⁵  Bing Pan⁵ 

[1] Department of Cardiology, Beijing Tian Tan Hospital, Capital Medical University, 100050, Beijing, China;Department of Cardiology, Beijing Tian Tan Hospital, Capital Medical University, 100050, Beijing, China;Tai Zhou Municipal Hospital, 318000, Taizhou, China;Department of Cardiovascular Medicine, Fujian Provincial Hospital, Fuzhou, China;Department of Nephrology, Union Hospital, Fujian Medical University Union Hospital, Fuzhou, China;The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, 100191, Beijing, China;

关键词: 15-oxo-ETE;    monocyte adhesion;    E-selectin;    Atherosclerosis;    PKC;   

DOI  :  10.1186/s12944-017-0518-2

 received in 2017-01-28, accepted in 2017-06-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundA great number of studies reported that 12/15-lipoxygenase (12/15-LO) played an important role in atherosclerosis. And its arachidonic acid(AA) metabolite, 15(S)-hydroperoxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15(S)-HETE), is demonstrated to mediate endothelial dysfunction. 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE) was formed from 15-hydroxyprostaglandin dehydrogenase (PGDH)-mediated oxidation of 15(S)-HETE. However, relatively little is known about the biological effects of 15-oxo-ETE in cardiovascular disease. Here, we explore the likely role of 15-lipoxygenase (LO)-1-mediated AA metabolism,15-oxo-ETE, in the early pathogenesis of atherosclerosis.MethodsThe 15-oxo-ETE level in serum was detected by means of liquid chromatography and online tandem mass spectrometry (LC-MS/MS). And the underlying mechanisms were illuminated by molecular techniques, including immunoblotting, MTT assay, immunocytochemistry and Immunohistochemistry.ResultsIncreased 15-oxo-ETE level is found in in patients with acute myocardial infarction (AMI). After 15-oxo-ETE treatment, Human umbilical vein endothelial cells (HUVECs) showed more attractive to monocytes, whereas monocyte adhesion is suppressed when treated with PKC inhibitor. In ex vivo study, exposure of arteries from C57 mice and ApoE−/−mice to 15-oxo-ETE led to significantly increased E-selectin expression and monocyte adhesion.ConclusionsThis is the first report that 15-oxo-ETE promotes early pathological process of atherosclerosis by accelerating E-selectin expression and monocyte adhesion. 15-oxo-ETE -induced monocyte adhesion is partly attributable to activation of PKC.

【 授权许可】

CC BY   
© The Author(s). 2017