Grant: Doctoral Research Award: Canada Graduate Scholarships

Challenges: Heart disease is a top cause of early death among women in Canada. Abnormal blood fat levels, like high cholesterol, can clog blood vessels. Like a clogged drain, clogged blood vessels block blood flow and increase chances of life-altering diseases like heart attacks and strokes. Sex influences these conditions, but research has been focused on men. This means we do not fully understand these conditions in women or provide the best treatments to improve their heart health. Goal: We want to understand how biological sex affects blood fat levels and clogged blood vessels. Estrogen is a natural chemical or sex hormone produced in the body. It helps protect heart health by lowering blood fat levels. Women normally have more estrogen than men, but this drops after menopause. Fat cells also influence blood fat levels. In obesity, fat cells can burst and release fat into the blood, like a water balloon bursting. A component called caspase-8 makes fat cells burst in mice. Researchers have shown that estrogen blocks components like caspase-8, but this has not been shown in fat cells yet. Approach: 1) We have special mice that do not have caspase-8 in their fat cells and fed them a diet that causes high blood fat levels and clogged blood vessels like humans. We expect the special mice to have lower blood fat levels and less clogged blood vessels compared to regular mice. This means caspase-8 worsens these conditions. 2) We will grow fat cells in a dish, remove caspase-8, and add estrogen, then measure fat cell bursting. We expect estrogen to reduce fat cell bursting caused by caspase-8. This means estrogen reduces blood fat levels by blocking caspase-8. Importance: This project will help explain how sex influences heart disease by showing that estrogen blocks caspase-8 in fat cells to lower blood fat levels. Knowing this, we can use caspase-8 as a heart disease risk indicator and make treatments that block caspase-8 to improve heart health for everyone.