Grant: Canada Postdoctoral Research Award (CPRA) program

Menopause, defined as 12 months of amenorrhea and ovarian cessation of estrogen and progesterone production, increases cardiovascular disease (CVD) risk in women, contributing to higher CVD mortality than men over the past 25 years. With life expectancy reaching 84 years, women may spend a significant portion of their lives in a high-risk postmenopausal state. Enlargement of the heart muscle, the main cause of heart failure, is closely linked to hormonal changes. Cytochrome P450 (CYP) enzymes break down important fats in cell membranes (arachidonic acid), producing metabolites known as epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs). These metabolites influence blood vessels, inflammation, and regulate heart cell function. Some exacerbate aging of the heart, causing it to enlarge abnormally and weaken, leading to heart failure. Women may experience these types of heart disease at age 50 and beyond because they lose the beneficial effects of sex hormones, mainly estrogen. Understanding these mechanisms is critical to developing sex-specific prevention strategies. What we will do: Human heart tissue will be obtained through the HOPE Program at the University of Alberta. We will investigate whether decreased hormones during menopause contribute to increased heart disease in women. Tissue from premenopausal and postmenopausal donors will be compared to measure changes in CYP enzymes and their lipid products (EETs/HETEs) using advanced LC-MS/MS techniques. We will also assess molecular and cellular markers of heart muscle enlargement. In parallel, human heart cells under low-hormone conditions that mimic menopause will be used to test whether adding estrogen or blocking specific CYP pathways prevents harmful changes. By combining findings from donor tissue and lab cells, we will identify key pathways that could be targeted to reduce menopause-related heart disease.