Epoxycyclopentenone-containing oxidized phospholipids restore endothelial barrier function via Cdc42 and Rac

Konstantin G. Birukov, Valery N. Bochkov, Anna A. Birukova, Kamon Kawkitinarong, Alexander Rios, Alexander Leitner, Alexander D. Verin, Gary M. Bokoch, Norbert Leitinger, Joe G.N. Garcia

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

After an acute phase of inflammation or injury, restoration of the endothelial barrier is important to regain vascular integrity and to prevent edema formation. However, little is known about mediators that control restoration of endothelial barrier function. We show here that oxidized phospholipids that accumulate at sites of inflammation and tissue damage are potent regulators of endothelial barrier function. Oxygenated epoxyisoprostane-containing phospholipids, but not fragmented oxidized phospholipids, exhibited barrier-protective effects mediated by small GTPases Cdc42 and Rac and their cytoskeletal, focal adhesion, and adherens junction effector proteins. Oxidized phospholipid-induced cytoskeletal rearrangements resulted in a unique peripheral actin rim formation, which was mimicked by coexpression of constitutively active Cdc42 and Rac, and abolished by coexpression of dominant-negative Rac and Cdc42. Thus, oxidative modification of phospholipids during inflammation leads to the formation of novel regulators that may be critically involved in restoration of vascular barrier function.

Original languageEnglish (US)
Pages (from-to)892-901
Number of pages10
JournalCirculation research
Volume95
Issue number9
DOIs
StatePublished - Oct 29 2004

Keywords

  • Actin cytoskeleton
  • Endothelial permeability
  • Mildly oxidized phospholipids
  • Small GTPases
  • Thrombin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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