U of A researchers receive grants from Heart & Stroke Foundation for “important, novel research” projects

The Heart & Stroke Foundation of Canada has awarded five research projects from the University of Alberta $300,000 each over the next three years for research in the areas of heart disease and stroke.

The foundation’s Grant-in-Aid (GIA) program provides operating funds to support “important, pertinent, novel research” in the areas of heart disease and stroke. According to the foundation’s website, GIA funding promotes research discovery, exploration and innovation across all health research themes.

A focus on youth and maternal health is a common theme in this year’s projects and of the five, three are led by researchers in the Department of Pediatrics. 

The projects: 

Lisa Hornberger - Department of Pediatrics

Vascular dysfunction in maternal heart disease & its contribution to adverse pregnancy outcomes

Hornberger’s study looks at heart disease in pregnant women, which accounts for a quarter of all pregnancy-related deaths. Specifically, the research will explore how the mother’s heart-muscle and blood-vessel health contribute to poor pregnancy outcomes and to the heart-muscle and blood-vessel health of her baby. This will be the first comprehensive study of the heart- and blood-vessel health of mothers with heart disease from early in the pregnancy. It will also be the first to examine how the heart and blood vessels adapt to the demands of pregnancy in the setting of underlying maternal heart disease with comparison to healthy pregnancies, and how for some women with heart disease, these normal adaptations do not occur due to underlying disease. 

“We are very grateful to the Heart & Stroke Foundation of Canada for their support,” said Hornberger. “Knowledge of mechanisms responsible for poor pregnancy outcomes among affected mothers is the first step to improving the health of their pregnancies and their infants.”

Michael Khoury - Department of Pediatrics

High intensity interval training (HITT) in youth with congenital heart disease: A randomized controlled trial of a novel telemedicine video game-linked exercise platform

Khoury’s project will examine whether a home-based HIIT program using a new device known as the MedBIKE™ can improve the exercise capacity of 10- to 18-year-olds with congenital heart disease (CHD). Khoury will also study whether this exercise program improves physical activity levels, quality of life and the health of the blood vessels of youth with CHD.

This will be the first study of its kind to look at HIIT in the CHD population, which is about one per cent of children born. Another unique feature of the study is the use of the MedBIKE™, a custom-made video game-linked bicycle designed by Khoury’s team that provides a continuous two-way video feed between the participant at home and a supervising health-care professional. No other studies in children with CHD have evaluated whether an exercise intervention can promote positive attitudes and changes in physical activity and exercise, and this research could potentially be expanded to other pediatric heart disease groups, such as those with heart failure and children who have received heart transplants.

“This funding will allow us to study home-based supervised exercise in children with heart disease, hopefully bringing us closer to bringing a program such as this to our patients here in Alberta,” said Khoury.

Gary Lopaschuk - Department of Pediatrics

Branched chain amino acid contribution to cardiac insulin resistance in heart failure

Scientists know that individuals who are obese or diabetic are at high risk for developing narrow blood vessels and have an increased risk of heart disease. It has also been shown that obesity and diabetes can directly compromise the ability of the heart muscle to contract properly, contributing to the development of heart failure. However, the exact reasons why heart function is compromised in these subjects is not known. Recent evidence suggests that an excessive use of branched chain amino acids by the heart may be an important contributor to abnormal heart function. 

Lopaschuk and team believe that in individuals with obesity or diabetes, excessive branched chain amino acids supplied to the heart can decrease its sugar use, which can decrease the ability of insulin to stimulate sugar metabolism by the heart in times of need. 

The team will explore the molecular mechanisms responsible for altered branch chain amino acid use in the hearts of subjects with obesity or diabetes, and how to inhibit fatty acid use by the heart to decrease the likelihood of developing heart failure. This could have a major impact on how patients with heart failure due to obesity and/or diabetes are treated in the future, potentially affecting hundreds of thousands of Canadians. 

“This funding should help us identify how alterations in cardiac energy metabolism contribute to the severity of heart failure, and allow us to identify new approaches to treat this debilitating disease," said Lopaschuk.

Craig Steinback - Faculty of Kinesiology, Sport and Recreation

Influence of advanced maternal age on cardiovascular structure, function and control

Steinback’s team—which includes FoMD’s Christy-Lynn Cooke and Sandra Davidge and the Faculty of Kinesiology, Sport and Recreation’s Margie Davenport—is studying why women who are 35 years old or older when they become pregnant have increased risk for pregnancy complications such as preeclampsia and gestational hypertension and worse pregnancy outcomes.

According to Steinback, pregnant women remain a significantly understudied population in health research. Further, there is a critical health gap in the understanding of women’s cardiovascular health during pregnancy, primarily because pregnant women have been excluded from nearly all clinical trials. However, Steinback’s interdisciplinary team believes that if they can identify mechanisms associated with cardiovascular health and disease during pregnancy, they will have the opportunity to develop interventions that provide a population level benefit and address that health gap. 

“We were very excited to receive funding for this project and are in the process of ramping up activities in the labs,” said Steinback. “Usually research happens in silos, or the translation between biomedical discovery research, early human investigations and clinical practice takes a significant amount of time and effort. We have brought these expertise together as part of one exciting project.”

Toshifumi Yokota - Department of Medical Genetics

Use of a T cell-derived peptide for delivery of antisense oligos to treat cardiomyopathy in muscular dystrophy

The objective of Yokota’s project is to develop a new delivery tool for antisense oligonucleotides, DNA-like molecules that were recently conditionally approved by the FDA to treat Duchenne muscular dystrophy (DMD). However, the drugs cannot treat the symptoms in the heart, as they are poorly taken up in the heart muscles and have little effectiveness in enhancing the lifespan of patients with DMD.

Yokota’s team recently discovered a type of delivery molecule that efficiently delivers DNA-like molecules to the heart muscle in fish and mice models. Preliminary data has already shown that these molecules target the gene products in both heart and body muscles with promising results. By advancing studies of a safe and effective class of drugs for heart delivery, Yokota hopes the work ultimately eases the burden on patients and families by helping to prolong and improve the quality of life of patients with DMD. Importantly, this delivery molecule could lead to the development and delivery of new drugs to treat many other forms of heart disease.

“Cardiac failure is a leading cause of death in many forms of muscular dystrophy,” said Yokota. “This grant will allow me to further develop effective therapy to protect heart muscle in muscular dystrophy using synthetic DNA-like molecules."