John Seubert

Summary:

Cardiovascular disease (CVD) is the leading cause of death in women. Importantly, women with CVD experience disproportionately higher mortality than men and yet our understanding of the differences is limited. Ischemic heart disease is a major contributor to CVD, yet development of successful therapies has remained elusive. Heart damage begins to occur after it has been deprived of oxygen (ischemia) for an extended period of time. While the immediate return of blood flow (reperfusion) to the heart is important, it too can damage the heart. Ischemia-reperfusion injury can significantly affect key components of the cardiac cells (cardiomyocytes), such as mitochondria. In the heart, mitochondria provide about 90% of the energy for cardiac muscle function. While the etiology of age-related cardiovascular pathogenesis is poorly understood, it has been shown that deterioration of mitochondria over time plays a critical role in age-related cardiac dysfunction. Mitochondria are critical to cardiomyocyte survival and heart function, so maintenance of a healthy mitochondrial population is essential for the preservation of healthy cardiac muscle. Dietary sources of essential fatty acids have a significant impact on cardiovascular health. The overall goal of my program is to investigate the cardioprotective role of novel metabolites produced from omega-3 and omega-6 fatty acids, which are found in dietary sources. Proteins within a cell metabolize these fatty acids into active molecules called epoxy lipids. These molecules are involved in regulating different functions in the body. Our research has demonstrated they can limit mitochondrial injury. We are interested in understanding how this occurs in aged females and whether targeting these molecules is a viable therapeutic approach to prevent and/or treat mitochondrial damage in aged women with CVD.