The average lifespan of Canadian women is 83.9 years. They tend to start menopause between the ages of 45 and 55, which means they can spend up to 40 per cent of their lives without the hormones estrogen and progesterone protecting their hearts. 

As a result, cardiovascular disease is the second leading cause of death in Canada, and more women than men die of it each year. Treatment with hormone replacement therapy is an option, but it comes with an elevated risk of breast cancer.

Now, a University of Alberta research team has been granted more than a million dollars by the Canadian Institutes of Health Research to search for and develop safer, more effective drugs to prevent heart disease in post-menopausal women.

“Hormone replacement therapy is not good for people who have a personal or family history of breast cancer because these hormones can cause breast cancer,” says principal investigator Ayman El-Kadi, professor and associate dean of research and graduate studies for Pharmacy and Pharmaceutical Sciences. “We’re trying to find a safer and more effective alternative that cannot cause breast cancer.”

El-Kadi and co-investigator Dion Brocks, professor of pharmacy and pharmaceutical sciences, are one of 19 U of A-based research teams to receive more than $16 million from the Canadian Institutes of Health Research through its Spring 2025 Project Grant competition.

 

The co-investigators will build on previous work to examine the role of a naturally produced enzyme called cytochrome P450, or CYP, in causing or protecting against cardiac hypertrophy during menopause. Hypertrophy is a thickening of the heart muscle that makes it harder to pump blood and can lead to heart failure. 

CYP regulates the production of hormones and other compounds like arachidonic acid, which the body turns into metabolites that are either protective or toxic to the heart. 

“We have already identified which compounds produced by the body are causing harm to the heart,” says El-Kadi. “Our preliminary data show that those compounds also play a significant role in cardiovascular disease during menopause.”

El-Kadi’s team has been working with a group of biochemists at the University of Texas to develop stable compounds that interfere with the body’s production of the harmful metabolites and encourage production of more protective metabolites. Multiple CYP-derived arachidonic acid metabolites are currently under investigation in human clinical trials.

“The drugs we are developing in Texas are similar to endogenous (naturally occurring) compounds, but there is a small modification so they cannot be degraded by the body,” explains El-Kadi. “They are similar to the good metabolites that are produced by the CYP but they are more stable, so they can be used as drugs.”

El-Kadi is also identifying and testing existing drugs that are currently used to treat other diseases to see whether they can be repurposed to treat heart disease in menopause. 

During the five-year grant period, the team will test the compounds in rats and in tissue donated by post-menopausal women who had heart disease. 

Along with the Texas collaborators, El-Kadi and Brocks are also working with U of A professors Jason Dyck and John Ussher, and three new PhD students will join the team. Ayman El-Kadi is a member of the Women and Children’s Health Research Institute, the Cardiovascular Research Institute and the Mazankowski Alberta Heart Institute. 

U of A researchers receive more than $16 million from CIHR

El-Kadi’s study is just one of 19 University of Alberta research projects from seven faculties that received new funding from CIHR in the Spring 2025 Project Grant competition:

Khaled Barakat, Faculty of Pharmacy & Pharmaceutical Sciences 
Assessing DGK Alpha as the key target for a promising immunomodulatory compound: Mechanism and implications in cancer immunotherapy
$738,226

Margie Davenport, Faculty of Kinesiology, Sport and Recreation
Co-principal applicants: Kari Bo, Norwegian School of Sport Sciences; Melanie Hayman, Central Queensland University; Tara-Leigh McHugh, University of Calgary
International practice and policy for pregnant and postpartum athletes
$100,000

Ayman El-Kadi, Faculty of Pharmacy & Pharmaceutical Sciences 
Role of cytochrome P450 enzymes in pathogenesis of cardiac hypertrophy during menopause
$1,032,750

Dean Eurich, School of Public Health
Co-principal applicants: Lynden Crowshoe, University of Calgary; Salim Samanani, OKAKI Health Intelligence Inc.; Chris Sarin, Indigenous Services Canada
Optimizing immunization coverage in First Nations communities in Alberta
$1,403,776

Elaine Hyshka, School of Public Health
Co-principal applicants: Kathryn Dong, Faculty of Medicine & Dentistry, Ginetta Salvalaggio, Faculty of Medicine & Dentistry, Shanell Twan, Boyle Street Community Services
Expanding compulsory drug treatment in Alberta: Perspectives of people who use drugs and health-care providers
$200,000

Roger Leng, Faculty of Medicine & Dentistry
Deciphering the USP7-UBE4B-p53 axis in cancer: Mechanistic insights and therapeutic opportunities
$650,250

Matthew Macauley, Faculty of Science
Elucidating the role of Siglec-G/-10 in the germinal centre
$983,026

Erin McCabe, Faculty of Rehabilitation Medicine
Co-principal applicants: Chester Ho, Faculty of Medicine & Dentistry; Kiran Manhas, Alberta Health Services; Maria Jose Lopez Parrilla (Santana), University of Calgary; Jennifer Zwicker, University of Calgary
Advancing Learning in Neurorehabilitation (ALIGN): Co-design, implementation and evaluation of a patient-centred measurement framework within a provincial learning health system
$596,701

Martin Munz, Faculty of Medicine & Dentistry
Embryonic cortical circuit development between neuronal classes, in vivo
$1,055,700

Vivian Mushahwar, Faculty of Medicine & Dentistry
Fully implantable intraspinal microstimulation system for restoring mobility after spinal cord injury
$1,388,476

Anna Phan, Faculty of Science
How social isolation alters the brain and behaviour
$757,350

Carla Prado, Faculty of Agricultural, Life & Environmental Sciences
Co-principal applicant: Rajavel Elango, University of British Columbia
Evaluating protein requirements in cancer survivorship: A novel evidence-based approach
$818,550

Georg Schmolzer, Faculty of Medicine & Dentistry
Co-principal applicants: Elizabeth Asztalos, Sunnybrook Research Institute; Po-Yin Cheung, Faculty of Medicine & Dentistry; Anup Katheria, The SHARP Foundation; Brenda Law, Faculty of Medicine & Dentistry; Mai Luu, Centre hospitalier universitaire Sainte-Justine; Gerhard Pichler, Medical University of Graz; Anne Solevaag, Oslo University Hospital; Pia Wintermark, Research Institute of the McGill University Health Centre; Maryna Yaskina, Women and Children’s Health Research Institute
Sustained inflation and chest compression versus 3:1 chest compression to ventilation ratio during cardiopulmonary resuscitation of asphyxiated newborns — SURV1VE-2-Trial
$1,155,152

Sangita Sharma, Faculty of Medicine & Dentistry
Co-principal applicants: Kukik Baker, Aqqiumavvik Arviat Wellness Society; Shirley Tagalik Aqqiumavvik, Arviat Wellness Society
Understanding human papillomavirus (HPV) vaccination and screening (including self-sampling) beliefs in Indigenous communities in Nunavut: A community-based and led, culturally safe, on-the-land approach
$100,000

Maya Shmulevitz, Faculty of Medicine & Dentistry
Molecular determinants of virus-sialic acid binding and its role in infection and dissemination at distinct niches
$1,357,876 

John Ussher, Faculty of Pharmacy & Pharmaceutical Sciences 
Co-principal applicant: Caroline Richard, Faculty of Agricultural, Life and Environmental Sciences
Immunometabolism as a mediator of differential outcomes regarding saturated versus unsaturated fat-based ketogenic diets in obesity
$810,900

Michael Weinfeld, Faculty of Medicine & Dentistry
Polynucleotide kinase/phosphatase: Its role in DNA strand break repair and a potential cancer therapeutic target
$1,005,976

Lori West, Faculty of Medicine & Dentistry
Overcoming ABO blood group inequity in transplantation: A new diagnostic assay to modernize ABO-incompatible organ transplantation
$1,071,000

Toshifumi Yokota, Faculty of Medicine & Dentistry
Advancing RNA splicing therapies for Duchenne muscular dystrophy: Optimizing multi-exon skipping strategies for broader clinical applicability
$986,850