Grant: CIHR Fellowship

Atherosclerosis, or the hardening of arteries, is the major cause of death worldwide, mainly due to heart attacks and strokes, and is the leading cause of heart failure that more than 600,000 people in Canada live with. Atherosclerosis is characterized by the build-up of low-density-lipoprotein cholesterol (LDL-C, also known as "bad cholesterol") and inflammatory cells in the arteries. This leads to the formation of atherosclerotic plaques that can potentially break, resulting in a blood clot that causes a heart attack or stroke. The Francis laboratory studies changes in the structure and cell composition of blood vessels like the coronary arteries that lead to plaque formation. They have made the ground-breaking discovery that the main place fats like cholesterol build up in arteries to form plaque are smooth muscle cells that line the arteries, not the white blood cells called macrophages that have long been believed to be the main site of cholesterol build-up. The purpose of this project is to study the genetic and phenotypic differences in smooth muscle cells and macrophages grown in dishes and collected from human coronary arteries of hearts. This will allow us (i) to elucidate how these cells contribute to the development and progression of atherosclerosis, (ii) to identify new pro- and anti-atherogenic cell markers, and (iii) to develop novel treatments to reduce the build-up of cholesterol in these cells. We hypothesize that foamy smooth muscle cells that contain cholesterol will further promote the development of atherosclerosis compared with macrophages. This is because smooth muscle cells do not easily release cholesterol from within the cell, and therefore are more likely to be resistant to current lipid-lowering treatments. This research is expected to lead to better comprehension of plaque formation in arteries and new ways to reduce heart attack, stroke, and heart failure in Canadians and throughout the world.