title: Platelet Inhibitors Reduce Rupture in a Mouse Model of Established Abdominal Aortic Aneurysm.
abstract: OBJECTIVE
  Rupture of abdominal aortic aneurysms causes a high morbidity and mortality in the elderly population. Platelet-rich thrombi form on the surface of aneurysms and may contribute to disease progression. In this study, we used a pharmacological approach to examine a role of platelets in established aneurysms induced by angiotensin II infusion into hypercholesterolemic mice.
  
  
  RESULTS
  Administration of the platelet inhibitors aspirin or clopidogrel bisulfate to established abdominal aortic aneurysms dramatically reduced rupture. These platelet inhibitors reduced abdominal aortic platelet and macrophage recruitment resulting in decreased active matrix metalloproteinase-2 and matrix metalloproteinase-9. Platelet inhibitors also resulted in reduced plasma concentrations of platelet factor 4, cytokines, and components of the plasminogen activation system in mice. To determine the validity of these findings in human subjects, a cohort of aneurysm patients were retrospectively analyzed using developed and validated algorithms in the electronic medical record database at Vanderbilt University. Similar to mice, administration of aspirin or P2Y12 inhibitors was associated with reduced death among patients with abdominal aortic aneurysm.
  
  
  CONCLUSIONS
  These results suggest that platelets contribute to abdominal aortic aneurysm progression and rupture.
authors.affiliation: Department of Medicine Division of Hematology and Oncology, UNC McAllister Heart Institute University of North Carolina at Chapel Hill Chapel Hill, NC 27599, USA.
authors.forename: A Phillip
authors.initials: AP
authors.lastname: Owens
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center Nashville, TN 37203.|Division of Epidemiology, Vanderbilt University Medical Center Nashville, TN 37203.
authors.forename: Todd L
authors.initials: TL
authors.lastname: Edwards
authors.affiliation: Department of Medicine Division of Hematology and Oncology, UNC McAllister Heart Institute University of North Carolina at Chapel Hill Chapel Hill, NC 27599, USA.
authors.forename: Silvio
authors.initials: S
authors.lastname: Antoniak
authors.affiliation: Department of Medicine Division of Hematology and Oncology, UNC McAllister Heart Institute University of North Carolina at Chapel Hill Chapel Hill, NC 27599, USA.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Geddings
authors.affiliation: Department of Cardiovascular Diseases John Ochsner Heart and Vascular Institute Ochsner Clinical School - The University of Queensland School of Medicine New Orleans, LA 70115.
authors.forename: Eiman
authors.initials: E
authors.lastname: Jahangir
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University Medical Center Nashville, TN 37203.
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: Wei
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University Medical Center Nashville, TN 37203.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Department of Medicine Division of Hematology and Oncology, UNC McAllister Heart Institute University of North Carolina at Chapel Hill Chapel Hill, NC 27599, USA.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Boulaftali
authors.affiliation: Department of Biochemistry and Biophysics, UNC McAllister Heart Institute University of North Carolina at Chapel Hill Chapel Hill, NC 27599, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bergmeier
authors.affiliation: Saha Cardiovascular Research Center University of Kentucky Lexington, KY 40536.
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center Nashville, TN 37203.|Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center Nashville, TN 37203.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center Nashville, TN 37203.
authors.forename: Uchechukwu K A
authors.initials: UKA
authors.lastname: Sampson
authors.affiliation: Department of Medicine Division of Hematology and Oncology, UNC McAllister Heart Institute University of North Carolina at Chapel Hill Chapel Hill, NC 27599, USA.
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D001019:Aortic Rupture / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000804:Angiotensin II
keywords: angiotensin II; aortic aneurysm, abdominal; aspirin; blood platelets; clopidogrel; mice