Journal
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
Volume 24, Issue 9, Pages 954-969Publisher
JAPAN ATHEROSCLEROSIS SOC
DOI: 10.5551/jat.37663
Keywords
Sphingosine 1-phosphate; Plasminogen activator inhibitor 1; Apolipoprotein M
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Funding
- JSPS KAKENHI [25253040, 15K15378, 16H06236]
- Charitable Trust Laboratory Medicine Research Foundation of Japan
- Banyu Life Science Foundation International
- CREST from JST/AMED
- Grants-in-Aid for Scientific Research [15H05897, 15K15378, 15H05906, 16H06236] Funding Source: KAKEN
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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. 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. 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-NF kappa B pathway. 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.
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