Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 35, Issue 9, Pages 2032-2041Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.115.305537
Keywords
angiotensin II; aortic aneurysm; abdominal; aspirin; blood platelets; clopidogrel; mice
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Funding
- National Institutes of Health [PO1-HL006350]
- National Institutes of Health NHLBI K99/R00 award [5K99-HL116786-02]
- American Heart Association [14BGIA20380134]
- National Center for Advancing Translational Sciences [5KL2RR024977]
- National Center for Advancing Translational Sciences
- Vanderbilt CTSA grant from NCATS/NIH [ULTR000445]
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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 P2Y(12) 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.
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