Lerner Research Institute News
Read about the latest advances from Lerner Research Institute scientists, including new findings, grant awards, innovations and collaborations.
Researchers to Study Link Between Platelets and Asymptomatic Abdominal Aortic Aneurysms
Dr. Cameron will study the mechanistic interaction between platelets and how they emerge as circulating biosensors, releasing proteins that are useful biomarkers for distinguishing fast- from slow-growing aneurysms.
Scott Cameron, MD, PhD, a researcher in the Department of Cardiovascular & Metabolic Sciences, has received a five-year, $2.6 million grant from the National Heart, Lung, and Blood Institute (part of the National Institutes of Health) to study the link between platelet activation and asymptomatic abdominal aortic aneurysms (AAA). The study aims to provide new methods to diagnose disease risk and promise for new medical therapies to treat AAA.
Abdominal aortic aneurysms are aortic dilations that afflict approximately one million elderly Americans and are the 13th leading cause of death in the United States. Most AAAs remain asymptomatic until rupture, which carries a 90% out-of-hospital mortality rate.
Patients treated with antiplatelet therapy may be protected from AAA
Dr. Cameron’s new study will build on previous research published in collaboration with Sean Lyden, MD, in the Journal of the American College of Cardiology that suggests patients treated with antiplatelet therapy are protected from AAA and aortic dissection and rupture, although the mechanisms behind these benefits remain unclear. Working with cardiothoracic and vascular surgery colleagues, Dr. Cameron discovered aneurysms and platelets react to one another in a loop-like configuration that contributes to blood vessel remodeling.
“The potential impact of this project is broad since strong preliminary data suggests circulating platelets communicate directly with the blood vessel wall and affect vessel function,” said Dr. Cameron, who is also section head of vascular medicine in the Miller Family Heart, Vascular & Thoracic Institute. “This knowledge, combined with what we’ve learned about a specific platelet receptor that may be a viable target for preventing blood clots, offers promise that the first medical therapy for asymptomatic AAA may be on the horizon.”
Receptor with potential as drug target
The Cameron team previously identified a protein on the surface of platelets that belongs to the olfactory receptor family that traditionally allows for the sense of smell. Dr. Cameron’s co-investigator A. Philip Owens, PhD, University of Cincinnati, earlier reported that patients with fast-growing AAA exhibit shed platelet surface proteins in their blood. This receptor could be capitalized on as a potential drug target in patients with aneurysms. Currently, no imaging technique or blood-based biomarker test has the capacity to identify this receptor.
With this new award, the Cameron team will test their hypothesis exploring the role platelets play as “biosensors” for limiting fast-growing AAA targets.
Using preclinical models, the researchers will assess AAA growth and rupture in the presence of drugs that inhibit known platelet receptors. The team will focus on the novel platelet olfactory receptor when biomechanically activated by a ligand discovered in Center for Therapeutics Discovery, which is directed by Shaun Stauffer, PhD. They will observe platelet surface receptors and determine those that most effectively activate platelets in developing AAA, then evaluate platelet-derived activity that contributes to aortic remodeling and AAA.
“This work promises a new medical therapy for treating patients with AAA to slow down aneurysmal growth,” said Dr. Cameron. “Since the treatment for AAA at this time is surgical, our work could greatly impact patient care.”
Image: Patient scan showing abdominal aorta and left/right iliac artery showing aortic dissection