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Updated: Nov 15, 2025

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
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A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors

Published on: June 8, 2022

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Sphingosine-1-phosphate: A mediator of the ARB-MI paradox?

Amin Polzin1, Carolin Helten1, Lisa Dannenberg1

  • 1Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich Heine University Hospital Düsseldorf, Düsseldorf, Germany.

International Journal of Cardiology
|March 6, 2021
PubMed

Insights

Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) affect sphingosine-1-phosphate (S1P) levels differently. ACEI treatment increased S1P, potentially explaining the ARB-MI paradox.

Area of Science:

  • Cardiovascular Disease Research
  • Pharmacology
  • Biochemistry

Background:

  • Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are crucial for cardiovascular disease prevention.
  • The "ARB-MI paradox" highlights a lack of myocardial infarction (MI) risk reduction in ARB-treated patients despite blood pressure control.
  • Sphingosine-1-phosphate (S1P) is a cardioprotective sphingolipid released by activated platelets.

Purpose of the Study:

  • To investigate differences in S1P homeostasis during ACEI/ARB treatment.
  • To explore the role of bradykinin and sphingosine kinases in ACEI/ARB-mediated S1P changes.
  • To generate a hypothesis for the ARB-MI paradox based on S1P metabolism.

Main Methods:

  • A pilot study involving 34 patients treated with ACEI or ARB.
  • Measurement of plasma S1P concentrations using liquid chromatography-tandem mass spectrometry before and after 3 months of treatment.
  • Quantification of bradykinin levels via enzyme-linked immunosorbent assay.

Main Results:

  • No significant difference in baseline S1P plasma concentrations between ACEI and ARB groups.
  • After 3 months, S1P levels were significantly higher in patients treated with ACEI compared to ARB (p=0.001).
  • No significant association was found between bradykinin and S1P levels, either before or after treatment.

Conclusions:

  • ACEI treatment leads to higher plasma S1P concentrations than ARB treatment.
  • Altered S1P metabolism may partially explain the ARB-MI paradox.
  • Further clinical trials are needed to validate these findings.
Abstract

Keywords:
ACEIARBPlatelet reactivityS1PThrombin

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