Libin Cardiovascular Institute researchers receive $2.5M in CIHR project grants

Four Libin Cardiovascular Institute researchers within the Cumming School of Medicine received nearly $2.5 million in project grants from the Canadian Institutes of Health Research in the latest grant announcement.

Drs. Xi-Long Zheng, PhD, Robert Sheldon, MD, PhD, Joon Lee, PhD, and David Campbell, MD, PhD, will now tackle their studies, which cover a range of topics from an enzyme’s role in the formation of abdominal aortic aneurysms to leveraging artificial intelligence techniques to transform treatment of coronary artery disease.

Libin Institute Director Paul Fedak, MD, PhD, is excited about the innovative research underway at the Institute.

“Our researchers are tackling numerous problems with the goal of improving outcomes for all cardiovascular patients,” he says. “Their use of cutting-edge techniques, willingness to collaborate, and passion for solving unanswered questions places Libin researchers amongst the top in the world. It’s an exciting time for cardiovascular research in Calgary.”

Abdominal aortic aneurysms

Zheng received $944,776 to investigate the role of the enzyme PCSK9 in the development of abdominal aortic aneurysms (AAA), a serious enlargement or bulge that can develop in the lower part of the aorta.

If these bulges — caused by the weakening of the aortic wall — rupture, they require major surgery and may lead to death. Symptoms of the developing aneurysm can be mild or non-existent. In fact, the first indication of AAA may be the sudden rupturing of the aorta.

Scientists know the development of AAA is tied to high blood pressure and atherosclerosis, the narrowing of the artery wall due to a buildup of plaque lesions on the walls of the vessels, which consist of smooth muscle cells. However, the molecular mechanisms behind the condition aren’t well understood.

Zheng notes that many researchers believe PCSK9’s association with accelerated cardiovascular disease is due to its strong association with high lipid levels, but he has a new hypothesis.

“We believe the enzyme is tied directly to the dysfunction of the smooth muscle cells that may lead to the development of AAA,” says Zheng, adding that previous work in the lab has shown PCSK9 causes death of the aortic smooth muscle cells, negatively impacts their contractability, and increases the levels of several enzymes responsible for breaking down the aortic structure.

Over the next five years, Zheng’s lab will look at the molecular mechanisms behind how PCSK9 induces the death of smooth muscle cells and how it breaks down tissue.

“We hope to discover a novel role for PCSK9 and find a new approach to prevent progression and rupture of abdominal aortic aneurysms,” says Zheng. “We are interested in the direct effects of PCSK9 on the cardiovascular system.”

Vasovagal syncope

Sheldon, a cardiologist and researcher, received $841,500 for his five-year study investigating the use of the drug, Atomoxetine, in preventing vasovagal syncope.

Vasovagal syncope is the most common cause of fainting, occurring with a specific trigger, such as at the sight of blood or when someone stands too long or is overheated.

According to Sheldon, some individuals faint multiple times each year, which puts them at risk of potentially serious injury.

“About half of the patients I see at my clinic suffer from this condition, and it can really impact their quality of life,” says Sheldon, noting there is a 15 per cent chance of injury each time someone faints.

Sheldon’s study, “Randomized, Prospective, Placebo-Controlled, Crossover Study of Atomoxetine in the Prevention of Vasovagal Syncope: The Seventh Prevention of Syncope Trial (POST7),” is one of several clinical trials looking at therapies to treat vasovagal syncope that he has led over the last two decades.

He hopes that Atomoxetine, which is used to treat attention deficit hyperactivity disorder, can be used to treat adults with frequent vasovagal syncope.

Other projects

Lee is leading a team of experts on a project with the goal of developing an artificial intelligence system that can provide treatment recommendations for coronary artery disease — the leading cause of death around the world — at the point of care. The project also aims to create guidelines that heart doctors can follow to effectively use the AI system in patient care.

The project taps into APPROACH, a data registry created at the University of Calgary in 1995 that has collected data from more than 300,000 Alberta patients with coronary artery disease.

Campbell is leading a project with the aim of showing that providing a healthy food subsidy to people with Type 2 diabetes and food insecurity will improve outcomes for this population. The one-year randomized trial seeks to demonstrate that the program will lead to improved blood sugar levels in those with diabetes, which will result in fewer complications, and savings for the public health system.

The research team includes decision-makers from the Ministry of Community and Social Services, Alberta Health Services and Alberta Blue Cross.