Reversal of thrombin-induced deactivation of CD39/ATPDase in endothelial cells by HMG-CoA reductase inhibition: Effects on Rho-GTPase and adenosine nucleotide metabolism

Nicole C. Kaneider, Petra Egger, Stefan Dunzendorfer, Patrizia Noris, Carlo L. Balduini, Donatella Gritti, Giovanni Ricevuti, Christian J. Wiedermann

Research output: Contribution to journalArticlepeer-review

Abstract

Adenosine triphosphate and diphosphate that activate platelet, leukocyte, and endothelium functions are hydrolyzed by endothelial CD39/ATPDase. Because CD39/ATPDase is downregulated in endothelial cells by inflammation and this may be affected by HMG-CoA reductase inhibitors, we examined the role of cerivastatin and simvastatin in regulation of endothelial CD39/ATPDase expression, metabolism of ATP/ADP, and function in platelets. Thrombin-stimulated endothelial cells in vitro were treated with the statins, and hydrolysis of exogenous ADP and ATP was assessed by high-performance liquid chromatography and malachite green assay. Platelet aggregation studies were performed with endothelial cell supernatants as triggers. CD39/ATPDase surface expression by endothelial cells was determined immunologically by fluorescence-activated cell sorter, mRNA expression by RT-PCR, and thrombin-induced dissociation of Rho-GTPases by Western blotting. Treatment by simvastatin or cerivastatin restored impaired metabolism of exogenous ATP and ADP in thrombin-activated endothelial cells by preventing thrombin-induced downregulation of CD39/ATPDase. In platelet aggregation studies, ATP and ADP supernatants of thrombin - activated endothelial cells were less stimulatory in the presence of statins than in their absence. Data show that statins preserve CD39/ATPDase activity in thrombin-treated endothelial cells involving alterations by statins of Rho-GTPase function and CD39/ATPDase expression. Preservation of adenine nucleotide metabolism may directly contribute to the observed anti-thrombotic and anti-inflammatory actions of statins.

Original languageEnglish
Pages (from-to)894-900
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number6
DOIs
Publication statusPublished - 2002

Keywords

  • Aggregation
  • Arterial thrombosis
  • Atherosclerosis
  • Thrombin
  • Vascular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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