CD40-ligand-dependent induction of COX-2 gene expression in endothelial cells by activated platelets: inhibitory effects of atorvastatin.
Increasing evidence shows the importance of platelet-endothelial cell interactions in the progression of atherosclerosis. Platelets contribute to coronary events both as major components of thrombi and as a triggering factor in inflammation that leads to plaque vulnerability. Recent data suggest that statins, besides their lipid-lowering properties, exert pleiotropic effects that may be beneficial in atherosclerosis. Whether activated platelets influence cyclooxygenase-2 (COX-2) expression in human umbilical vein endothelial cells (HUVEC), the effect of atorvastatin, and possible mechanisms were investigated. COX-2 gene expression in HUVEC was studied using real-time polymerase chain reaction. CD40 ligand surface expression of platelets was tested by fluorescence-activated cell sorting analyses. Activated platelets significantly up-regulated COX-2 gene expression in HUVEC. Co-incubation of platelets with atorvastatin was shown to reverse this up-regulation via reduction of CD40 ligand surface expression on platelets. Data suggest that atorvastatin influences CD40-CD40-ligand-dependent platelet-endothelial interaction and that this influence affects platelet-induced COX-2 expression in HUVEC.
Mosheimer
Birgit A
BA
Division of General Internal Medicine, Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria.
Kaneider
Nicole C
NC
Feistritzer
Clemens
C
Djanani
Angela
A
Sturn
Daniel H
DH
Patsch
Josef R
JR
Wiedermann
Christian J
CJ
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000188:drug therapy / Q000503:physiopathology; D000069059:Atorvastatin; D001792:Blood Platelets / Q000502:physiology*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000096:biosynthesis*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins; D015539:Platelet Activation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011758:Pyrroles / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D019013:CD40 Antigens; D006538:Heptanoic Acids; D008565:Membrane Proteins; D011758:Pyrroles; D023201:CD40 Ligand; D000069059:Atorvastatin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases