https://scholars.lib.ntu.edu.tw/handle/123456789/627712
標題: | Inhibition of semicarbazide-sensitive amine oxidase reduces atherosclerosis in apolipoprotein E-deficient mice | 作者: | SHU-HUEI WANG Yu, Tse-Ya FENG-CHIAO TSAI Weston, Chris J MAO-SHIN LIN CHI-SHENG HUNG HSIEN-LI KAO Li, Yu-I Solé, Montse Unzeta, Mercedes YUH-LIEN CHEN LEE-MING CHUANG HUNG-YUAN LI |
關鍵字: | VASCULAR ADHESION PROTEIN-1; SMOOTH-MUSCLE-CELLS; DEPENDENT DIABETES-MELLITUS; LIPOPROTEIN METABOLISM; END-PRODUCTS; OXIDIZED LDL; INFLAMMATION; INVOLVEMENT; OVEREXPRESSION; CONSEQUENCES | 公開日期: | 七月-2018 | 出版社: | ELSEVIER SCIENCE INC | 卷: | 197 | 起(迄)頁: | 12 | 來源出版物: | Translational research : the journal of laboratory and clinical medicine | 摘要: | Inflammation, oxidative stress, and formation of advanced glycated end products (AGEs) and advanced lipoxidation end products (ALEs) are important for atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation and has semicarbazide-sensitive amine oxidase (SSAO) activity, which catalyzes oxidative deamination to produce hydrogen peroxide and aldehydes, leading to generation of AGEs and ALEs. However, the effect of VAP-1/SSAO inhibition on atherosclerosis remains controversial, and no studies used coronary angiography to evaluate if plasma VAP-1/SSAO is a biomarker for coronary artery disease (CAD). Here, we examined if plasma VAP-1/SSAO is a biomarker for CAD diagnosed by coronary angiography in humans and investigated the effect of VAP-1/SSAO inhibition by a specific inhibitor PXS-4728A on atherosclerosis in cell and animal models. In the study, VAP-1/SSAO expression was increased in plaques in humans and in apolipoprotein E (ApoE)-deficient mice, and colocalized with vascular endothelial cells and smooth muscle cells (SMCs). Patients with CAD had higher plasma VAP-1/SSAO than those without CAD. Plasma VAP-1/SSAO was positively associated with the extent of CAD. In ApoE-deficient mice, VAP-1/SSAO inhibition reduced atheroma and decreased oxidative stress. VAP-1/SSAO inhibition attenuated the expression of adhesion molecules, chemoattractant proteins, and proinflammatory cytokines in the aorta, and suppressed monocyte adhesion and transmigration across human umbilical vein endothelial cells. Consequently, the expression of markers for macrophage recruitment and activation in plaques was decreased by VAP-1/SSAO inhibition. Besides, VAP-1/SSAO inhibition suppressed proliferation and migration of A7r5 SMC. Our data suggest that plasma VAP-1/SSAO is a novel biomarker for the presence and the extent of CAD in humans. VAP-1/SSAO inhibition by PXS-4728A is a potential treatment for atherosclerosis. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627712 | ISSN: | 1931-5244 | DOI: | 10.1016/j.trsl.2018.03.001 |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。