Platelets as Biosensors and Mediators of Aortic Aneurysm Growth

Project Summary
Asymptomatic abdominal aortic aneurysms (AAA) can progress to rupture with an out-of-hospital
mortality of 90%. Accelerated AAA growth is associated with platelet activation and platelet
aggregates (thrombi) in aneurysmal segments. Antiplatelet drugs may limit AAA growth and rupture
risk. A mechanistic explanation for these observations has never been elucidated. This project builds
upon our discovery that platelets from patients with AAA are hyperactivated through selective surface
receptors and that the antiplatelet drug aspirin partially inhibits AAA growth and rupture. This
suggests a new link between platelet activation and aneurysm development, and implies aspirin may
not be the best antiplatelet drug to suppress. aneurysm growth. Using an ex vivo system to
recapitulate disturbed (turbulent) blood flow in aneurysmal arteries, localization of an olfactory
receptor on the surface of the platelet membrane is a new and promising target to suppresses AAA
growth. Discovering this pathway in platelets from patients with AAA exposed to turbulent blood flow
is a conceptual advancement in our understanding of how platelets mechanically sense and respond
to their external environment. Platelets therefore emerge as circulating biosensors, releasing proteins
that are useful biomarkers for distinguishing fast from slow-growing aneurysms. This project offers
the promise of the first medical therapy to treat AAA.

Grant Number: 5R01HL158801-05
NIH Institute/Center: NIH
Principal Investigator: Scott Cameron