Vehicle-dependent Effects of Sphingosine 1-phosphate on Plasminogen Activator Inhibitor-1 Expression
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- Takahashi Chiharu
- Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo CREST, Japan Science and Technology Corporation (JST)
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- Kurano Makoto
- Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo CREST, Japan Science and Technology Corporation (JST)
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- Nishikawa Masako
- Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo CREST, Japan Science and Technology Corporation (JST)
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- Kano Kuniyuki
- CREST, Japan Science and Technology Corporation (JST) Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
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- Dohi Tomotaka
- Department of Cardiovascular Medicine, Juntendo University School of Medicine
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- Miyauchi Katsumi
- Department of Cardiovascular Medicine, Juntendo University School of Medicine
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- Daida Hiroyuki
- Department of Cardiovascular Medicine, Juntendo University School of Medicine
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- Shimizu Tomo
- Tsukuba Research Institute, Research & Development Division, Sekisui Medical Co., Ltd.
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- Aoki Junken
- CREST, Japan Science and Technology Corporation (JST) Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
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- Yatomi Yutaka
- Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo CREST, Japan Science and Technology Corporation (JST)
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Abstract
<p>Aim: Sphingosine 1-phosphate (S1P) has been suggested to be a positive regulator of plasminogen activator inhibitor 1 (PAI-1) in adipocytes, while some studies are not consistent with this prothrombotic property of S1P. Since S1P is bound to apolipoprotein M (apoM) on HDL or to albumin in plasma, we compared the properties of these two forms on the PAI-1 induction.</p><p>Methods: We investigated the associations of S1P, apoM, and PAI-1 concentrations in the plasma of normal coronary artery (NCA), stable angina pectoris (SAP), and acute coronary syndrome (ACS) subjects (n=32, 71, and 38, respectively). Then, we compared the effects of S1P with various vehicles on the PAI-1 expression in 3T3L1 adipocytes. We also investigated the modulation of the PAI-1 levels in mice infected with adenovirus coding apoM.</p><p>Results: Among ACS subjects, the PAI-1 level was positively correlated with the S1P level, but not the apoM level. In adipocytes, S1P bound to an apoM-rich vehicle induced PAI-1 expression to a lesser extent than the control vehicle, while S1P bound to an apoM-depleted vehicle induced PAI-1 expression to a greater extent than the control vehicle in 3T3L1 adipocytes. Additionally, apoM overexpression in mice failed to modulate the plasma PAI-1 level and the adipose PAI-1 expression level. S1P bound to albumin increased PAI-1 expression through the S1P receptor 2-Rho/ROCK-NFκB pathway.</p><p>Conclusion: S1P bound to albumin, but not to apoM, induces PAI-1 expression in adipocytes, indicating that S1P can exert different properties on the pathogenesis of vascular diseases, depending on its vehicle.</p>
Journal
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- Journal of Atherosclerosis and Thrombosis
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Journal of Atherosclerosis and Thrombosis 24 (9), 954-969, 2017
Japan Atherosclerosis Society