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.

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.

• Authors: A Phillip Owens 3rd, Todd L Edwards, Silvio Antoniak, Julia E Geddings, Eiman Jahangir, Wei-Qi Wei, Joshua C Denny, Yacine Boulaftali, Wolfgang Bergmeier, Alan Daugherty, Uchechukwu K A Sampson, Nigel Mackman
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 35 Issue 9 Pg. 2032-2041 (Sep 2015) ISSN: 1524-4636 [Electronic] United States
• PMID: 26139462 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Platelet Aggregation Inhibitors
• Angiotensin II

Topics

• Aged
• Angiotensin II (toxicity)
• Animals
• Aorta, Abdominal (metabolism, pathology)
• Aortic Aneurysm, Abdominal (blood, chemically induced, prevention & control)
• Aortic Rupture (blood, chemically induced, prevention & control)
• Disease Models, Animal
• Female
• Follow-Up Studies
• Humans
• Infusions, Intravenous
• Male
• Mice
• Mice, Inbred C57BL
• Platelet Aggregation Inhibitors (administration & dosage)