U of A researcher’s goal is to develop therapies that prevent and treat cardiac injury and improve overall cardiac health, particularly in older people

John Seubert’s research has evolved over the past 25 years — from aquatic toxicology to investigating the impact that aging has on the heart and how omega-3 fatty acids might help protect it.

08 February 2023

John Seubert is a professor in the University of Alberta’s Faculty of Pharmacy and Pharmaceutical Sciences and an adjunct professor in the Faculty of Medicine & Dentistry, Department of Pharmacology. He has recently received a grant-in-aid award from Heart & Stroke for his research project investigating the protective role of essential fatty acids on the aging heart and hopes his research will lead to developments that prevent and treat heart damage and improve overall cardiac health, particularly in older people.

To celebrate Heart Month (February) the College of Health Sciences caught up with Seubert to learn more about him and his work. Here is what we found out.

What is the focus of your research?

Dietary sources of fatty acids are known to have a significant effect on cardiovascular health, but many of the benefits are poorly understood. We focus on specific cytochrome P450 metabolites — called epoxylipids — that are derived from essential fatty acids. These compounds are generated within the cell and can act as lipid mediators regulating cellular function.
Older individuals comprise more than 75 per cent of patients with cardiovascular disease, yet most of the basic research utilizes young animal models. We are interested in the questions this raises regarding the development of therapies. Recently, we have begun investigating the impact that aging has on the heart and how epoxylipids can limit injury.

While the cause of age-related cardiovascular disease development is poorly understood, the deterioration of key cellular organelles, such as mitochondria, plays a critical role. Mitochondria are vital to the survival and function of the heart, so maintenance of a healthy mitochondrial population is essential for the preservation of a healthy heart. We are working to understand the fundamental mechanisms of how these epoxylipids can protect mitochondrial quality following cardiac injury, notably in aged hearts.

Why is your research important?

Cardiovascular diseases remain a leading cause of morbidity and mortality where injury caused by ischemia (oxygen deprivation) accounts for a majority of the adverse effects. Heart damage begins to occur after it has been deprived of oxygen for an extended period of time. Although mortality rates have decreased over the last 30 years, myocardial ischemic injury (MI) remains a critical problem. Due to the irreversible cardiac damage caused by MI, as many as 30 to 40 per cent of heart attack survivors progress to heart failure.

Ischemic injury can significantly affect key components of the cell, such as mitochondria. In the heart, mitochondria provide about 90 per cent of the energy for cardiac function. Significant damage caused by ischemic injury can impact the energy production of the cell, resulting in dysfunction and cell death in the heart. This cell death is the main pathology associated with heart attacks, heart failure or sudden death. Therefore, targeting strategies that reduce mitochondrial damage is important.

What sort of impact do you hope your research will make?

The overall goal of this project is to investigate the protective role of fatty acids in the heart, specifically omega-3 fatty acids. These molecules are obtained from the diet but can be found in the membranes of cells in an inactive state. Proteins found in the body will break it down into active molecules. The cytochrome P450 epoxygenases are proteins involved in this process. They generate products called epoxydocosapentaenoic acids (EDPs).

The EDPs are involved in regulating different functions in the body. Our preliminary data demonstrate that EDPs will protect mitochondria and the heart against injury. Our research investigates how this occurs in the aged heart. The anticipated results will provide valuable information in the development of treatments for heart disease.

How do you conduct your research?

We previously discovered novel information about mitochondrial health in our mouse models that have increased levels of EDPs. Now we are employing both genetic animal models and pharmacological approaches to examine the protective effects of EDPs on preserving mitochondria in the heart and how the protection impacts heart function and recovery from injury. Animal cell-culture experiments examine the more specific details of how EDPs activate protective signals in the heart that reduce mitochondrial damage.

What led you to this area of study?

My path leading to this area of research began in graduate school, where I studied aquatic toxicology, and has evolved over the past 25 years, moving me across the country, into the United States for a postdoctoral fellowship and finally to the University of Alberta. A central theme has always been my interest in understanding the role the cytochrome P450 system has within the cell to assist in the development of novel drug targets and strategies to limit injury and improve health.

What are the most rewarding and the most challenging aspects of your work?

The most rewarding aspect of my work is seeing the progression and success of trainees and the publication of our research. The most challenging aspect is securing resources to make sure we are successful.

What is something your colleagues would be surprised to learn about you?

I competed in flatwater sprint kayaking at the Canada Summer Games.

What's the No. 1 piece of advice you give your grad students?

Research is slow with many ups and downs; often you can learn a lot when your hypothesis or experiments do not produce the results you predicted. So you need to be patient, think outside the box and work hard.