Research News

Joint research from Cleveland Clinic and the University of Cincinnati has identified a new biomarker for abdominal aortic aneurysm screening that is found in platelets. Investigators also found the protein GPVI can serve as a potential therapeutic target for stopping an aneurysm from growing.

Abdominal aortic aneurysm (AAA) affects over 1 million American adults, typically over the age of 65 and with a 90% out-of-hospital mortality rate. Currently, surgical removal for large or rapidly expanding aneurysms is the only way to prevent aortic rupture.

“Discovering this critical role the GPVI protein plays with AAA opens up the possibility of developing a therapeutic that could halt the growth of the aneurysm and avoid risky surgery of the aorta,” says Scott Cameron, MD, PhD, a principal investigator and cardiologist at Cleveland Clinic. “As of now, there are no treatment options other than surgery, so that would be transformative for the field.”

Dr. Cameron partnered with Phillip Owens, PhD, a researcher at University of Cincinnati, on a study that examined the platelet activity of GPVI in two independent AAA patient cohorts in Europe and at Cleveland Clinic. Findings published in Blood showed GPVI levels in bloodwork are highly predictive of an AAA diagnosis and are more strongly associated with aneurysm growth rate compared to the current “gold standard” biomarker, the protein D-dimer. GPVI blood level measurements also indicated whether the aneurysm was slow or fast-growing — vital for determining patient risk and treatment options.

Currently, if AAA is detected before rupture, it’s almost always by chance. In many cases, a patient goes to the ER with stomach pain or an unrelated abdominal issue, receives an imaging scan and an aneurysm is detected in the results. Slow-growing aneurysms can develop in someone’s system for more than a decade and oftentimes remain completely undetected until it’s too late.

"We can't predict who in the human population is going to get an AAA," Dr. Owens explains. "Most of them are thought to be spontaneous, while few are thought to be purely genetic — and even then, it's a percentage game. It's a very tricky disease to diagnose."

A shared interest leads to discovery

Dr. Cameron and Dr. Owens first met at a platelet conference in 2015 where they both presented, albeit on different topics — Dr. Owens’ focus was on AAA and Dr. Cameron’s was on the protein ERK5’s role in heart disease. Once their talks concluded, Dr. Cameron complimented Dr. Owens on his aneurysm presentation. After just a brief conversation, they formed an immediate bond over their shared interest in the topic and their respective experience with platelet-orientated and coagulation-driven diseases. In the months that followed, Dr. Owens increasingly found himself seeking out Dr. Cameron’s perspective.

“There were, and still are, very few people in the country who are looking at the hemostasis and platelet aspects of AAA,” Dr. Owens explains. “Most are more interested in the heavy immune-cell, aortic architecture and vascular cells. This shared research area between Dr. Cameron and me made it clear that we should work together.”

Dr. Cameron and Dr. Owens previously established other therapeutic targets based on platelet interactions; a parallel observation to the most recent study showed that an olfactory membrane receptor is a target for treating AAA through suppressing platelet reactivity. Dr. Owens says that the pair work “in tandem,” with Dr. Cameron’s clinical experience complimenting his basic research background.

“Dr. Cameron has become one of my closest collaborators. Science is a competitive field, and everyone is always trying to beat everyone else to the first publication and the novel story,” Dr. Owens said. “It is exceedingly rare to have a colleague with whom you can be completely open. I was happy to welcome Dr. Cameron into the field of platelets and AAA. There’s plenty of room in the sandbox for all of us.”

The investigation into GPVI was sparked by yet another collaborator: University of Rochester’s Doran Mix, MD. He brought to the lab a section of an aorta that had thrombus (a blood clot), which had been extracted from a patient after surgery. Dr. Owens profiled the genes in the blood vessel wall and in the thrombus and compared them to the genes in platelets from other patients with known aneurysms. GPVI was present in platelets, the thrombus and the blood vessel wall. That's when Dr. Owens and Dr. Cameron began to wonder if GPVI played a role in the growth of aneurysms.

The path ahead for improving abdominal aortic aneurysm screening

Dr. Owens and Dr. Cameron used the data from a cohort of European AAA patients to develop a blood test that measures GPVI in a patient's blood. The measured level of the protein would indicate whether the patient has a slow or fast-growing aneurysm and how quickly the patient needed surgery.

“The results of our study with the European cohort were very promising, but it was clear we needed to perform some further studies to confirm it — the data seemed almost too good to be true,” Dr. Cameron recalls. “So, in 2023 we repeated the trial with about 300 Cleveland Clinic patients who were known to have AAA. This trial further confirmed that GPVI functioned as a biomarker and potential drug target for AAA. The future implications of this on patient care are remarkable.”

Work is already underway for Dr. Cameron and Dr. Owens to outline the biological processes that result in GPVI levels as a biomarker. This means looking at interactions on a molecular level between aneurysm growth and the degree of GPVI sheared from platelets into the blood that distinguishes slow from fast AAA growth. The labs have also started looking for new biomarkers that function similarly to GPVI. They envision a screening process that would combine several of these potent biomarkers into a panel that could be used on patients over the age of 50 to proactively find AAA.

“As a cardiologist, I witness firsthand my patients’ fear when they learn they have an AAA and may have to undergo risky surgery to remove it,” Dr. Cameron says. “The availability of a simple blood test that would diagnose the presence and size of an aneurysm and the possibility of administering a treatment to halt that growth, would be groundbreaking for this complicated disease.”