Platelet inhibitors reduce rupture in a mouse model of established abdominal aortic aneurysm

Owens, A. Phillip, Edwards, Todd L., Antoniak, Silvio, Geddings, Julia E., Jahangir, Eiman, Wei, Wei-Qi, Denny, Joshua C., Boulaftali, Yacine, Bergmeier, Wolfgang, Daugherty, Alan, Sampson, Uchechukwu K. A. and MacKman, Nigel (2015) Platelet inhibitors reduce rupture in a mouse model of established abdominal aortic aneurysm. Arteriosclerosis, Thrombosis, and Vascular Biology, 35 9: 2032-2041. doi:10.1161/ATVBAHA.115.305537


Author Owens, A. Phillip
Edwards, Todd L.
Antoniak, Silvio
Geddings, Julia E.
Jahangir, Eiman
Wei, Wei-Qi
Denny, Joshua C.
Boulaftali, Yacine
Bergmeier, Wolfgang
Daugherty, Alan
Sampson, Uchechukwu K. A.
MacKman, Nigel
Title Platelet inhibitors reduce rupture in a mouse model of established abdominal aortic aneurysm
Journal name Arteriosclerosis, Thrombosis, and Vascular Biology   Check publisher's open access policy
ISSN 1079-5642
1524-4636
Publication date 2015-09-28
Year available 2015
Sub-type Article (original research)
DOI 10.1161/ATVBAHA.115.305537
Volume 35
Issue 9
Start page 2032
End page 2041
Total pages 10
Place of publication Philadelphia, PA United States
Publisher Lippincott Williams and Wilkins
Collection year 2016
Language eng
Formatted 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.

Approach and 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.
Keyword Angiotensin II
Aortic aneurysm, abdominal
Aspirin
Blood Platelets
Clopidogrel
Mice
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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