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Hypertension is associated with marked alterations in sphingolipid biology: a potential role for ceramide

Léon J A Spijkers1, Rob F P van den Akker, Ben J A Janssen

  • 1Department of Pharmacology and Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands.

Plos One
|August 6, 2011
PubMed

Insights

Hypertension alters sphingolipid biology, increasing ceramide levels and vascular tone. This study found elevated ceramide in hypertensive rats and humans, contributing to increased blood pressure.

Area of Science:

  • Cardiovascular Biology
  • Lipid Metabolism
  • Hypertension Pathophysiology

Background:

  • Hypertension is characterized by endothelial dysfunction and vascular remodeling.
  • Sphingolipids regulate vascular contractility and growth, suggesting a role in hypertension.

Purpose of the Study:

  • To investigate alterations in sphingolipid biology in hypertension.
  • To determine if these changes affect vascular function.

Main Methods:

  • Used spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.
  • Administered sphingosine kinase inhibitor (dimethylsphingosine) and sphingomyelinase.
  • Performed imaging mass spectrometry, immunohistochemistry, and lipidomics analysis.
  • Measured blood pressure and vascular contractility.

Main Results:

  • Shifting the ceramide/S1P ratio induced contractions in SHR but not WKY vessels.
  • Ceramide mediated these contractions, involving iPLA(2), cyclooxygenase-1, and thromboxane synthase.
  • Dimethylsphingosine increased blood pressure in SHR but not WKY rats.
  • Elevated ceramide levels were found in SHR arterial tissue and plasma, and in human hypertensive patients.

Conclusions:

  • Hypertension is linked to significant changes in vascular sphingolipid biology, notably increased ceramide.
  • Elevated ceramide levels and signaling contribute to increased vascular tone in hypertension.
  • These findings highlight sphingolipids as potential therapeutic targets for hypertension.
Abstract

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