Vehicle-dependent effects of sphingosine 1-phosphate on plasminogen activator inhibitor-1 expression

Chiharu Takahashi, Makoto Kurano, Masako Nishikawa, Kuniyuki Kano, Tomotaka Dohi, Katsumi Miyauchi, Hiroyuki Daida, Tomo Shimizu, Junken Aoki, Yutaka Yatomi

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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 pro-thrombotic 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-NFκB 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.

Original languageEnglish
Pages (from-to)954-969
Number of pages16
JournalJournal of atherosclerosis and thrombosis
Issue number9
Publication statusPublished - 2017


  • Apolipoprotein M
  • Plasminogen activator inhibitor 1
  • Sphingosine 1-phosphate

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical


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