Activation of group VI phospholipase A 2 isoforms in cardiac endothelial cells

Janhavi Sharma, John Turk, David J. Mancuso, Harold F. Sims, Richard W. Gross, Jane McHowat

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The endothelium comprises a cellular barrier between the circulation and tissues. We have previously shown that activation of proteaseactivated receptor 1 (PAR-1) and PAR-2 on the surface of human coronary artery endothelial cells by tryptase or thrombin increases group VIA phospholipase A 2 (iPLA 2β) activity and results in production of multiple phospholipid-derived inflammatory metabolites. We isolated cardiac endothelial cells from hearts of iPLA 2β-knockout (iPLA 2β-KO) and wild-type (WT) mice and measured arachidonic acid (AA), prostaglandin I 2 (PGI 2), and platelet-activating factor (PAF) production in response to PAR stimulation. Thrombin (0.1 IU/ml) or tryptase (20 ng/ml) stimulation of WT endothelial cells rapidly increased AA and PGI 2 release and increased PAF production. Selective inhibition of iPLA 2β with (S)-bromoenol lactone (5 μM, 10 min) completely inhibited thrombin- and tryptase-stimulated responses. Thrombin or tryptase stimulation of iPLA 2β-KO endothelial cells did not result in significant PAF production and inhibited AA and PGI 2 release. Stimulation of cardiac endothelial cells from group VIB (iPLA 2γ)-KO mice increased PAF production to levels similar to those of WT cells but significantly attenuated PGI 2 release. These results indicate that cardiac endothelial cell PAF production is dependent on iPLA2β activation and that both iPLA 2β and iPLA 2β may be involved in PGI 2 release.

Original languageEnglish
Pages (from-to)C872-C879
JournalAmerican Journal of Physiology - Cell Physiology
Volume300
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • Endothelium
  • Platelet-activating factor
  • Prostacyclin

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