title: Inhibition of arterial thrombosis by recombinant annexin V in a rabbit carotid artery injury model.
abstract: BACKGROUND
  The procoagulant effect of anionic phospholipid may play a major role in the development of arterial thrombosis.
  
  
  RESULTS
  Annexin V, a calcium-dependent anionic-phospholipid-binding protein, was expressed and isolated from Escherichia coli and its antithrombotic effect examined in a rabbit carotid artery thrombosis model. A partially occlusive thrombus was formed in the left carotid artery by application of electric current to produce an approximately 50% occlusion of the lumen. After the current was discontinued, flow ceased completely within 42+/-12 minutes (n=6) because of continuing platelet/fibrin thrombus formation. When annexin V was given at doses of 2.8 to 16.6 microg x kg(-1) x min(-1) for a period of 180 minutes, starting at the time the current was stopped, there was a dose-dependent inhibition of thrombus formation. At a dose of 5.6 microg x kg(-1) x min(-1), blood flow remained patent throughout the infusion and for an additional 60 minutes after the infusion was stopped. In addition, there was a decrease in thrombus weight (16+/-7.4 versus 2.0+/-1.0 g), (125)I-fibrin deposition (approximately 45% reduction, P<.001), and (111)In-labeled platelet accumulation (approximately 43% reduction, P<.001). Prior mixing of annexin V with phosphatidylserine micelles abolished the antithrombotic effect of annexin V, whereas mixing with phosphatidylcholine micelles had no effect. The antithrombotic effect of annexin V was not associated with bleeding tendency, as judged by the amount of blood absorbed in a gauze pad placed in a surgical incision extending to the muscle tissue and by the standard template bleeding time.
  
  
  CONCLUSIONS
  These observations support a potentially important role for anionic phospholipid exposure in platelets in arterial thrombosis, and inhibition of this activity could be a novel target for therapy in coronary thrombosis and stroke and after angioplasty.
authors.affiliation: Department of Internal Medicine, University of Texas Health Science Center, Houston, USA.
authors.forename: P
authors.initials: P
authors.lastname: Thiagarajan
authors.forename: C R
authors.initials: CR
authors.lastname: Benedict
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002339:Carotid Arteries / Q000473:pathology / Q000648:ultrastructure; D020212:Carotid Artery Injuries; D002341:Carotid Artery Thrombosis / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D003001:Cloning, Molecular; D004337:Drug Carriers; D004558:Electric Stimulation; D004926:Escherichia coli; D005337:Fibrin / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008297:Male; D008855:Microscopy, Electron, Scanning; D010314:Partial Thromboplastin Time; D010718:Phosphatidylserines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000276:immunology; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D017304:Annexin A5; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D010718:Phosphatidylserines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D005337:Fibrin; D006493:Heparin