Grant: Operating Grant

Cardiovascular disease is the leading cause of death in Canada. High blood cholesterol is a risk factor for cardiovascular diseases. Studies have shown that daily intake of plant sterols or ezetimibe can lower blood cholesterol concentrations. It is unknown whether plant sterols and ezetimibe have different mechanisms of action on cholesterol metabolism. Studying individuals with a rare disease such as sitosterolemia provides important insight into the mechanisms underlying cardiovascular disease risks. Sitosterolemia is a genetic disease caused by a defect in the genes that code for proteins that normally carry plant sterols out of the body. Homozygous sitosterolemia is characterized by high accumulation of blood cholesterol and plant sterol levels which can lead to atherosclerosis at an early age and high risk for heart attack. The current treatment of choice for homozygous sitosterolemia is the drug ezetimibe. Compared to individuals with homozygous sitosterolemia, people with heterozygous sitosterolemia are not clinically sick but may have increased blood cholesterol concentration. Studies in people with homozygous and heterozygous sitosterolemia will help us to better understand how plant sterols affect cholesterol function in the body to reduce cardiovascular disease risk. The main goals of this research are, therefore, to (a) study the effects of plant sterol intake on blood plant sterol, and cholesterol concentration and metabolism in individuals with heterozygous sitosterolemia compared to non-carriers; and (b)study the effects of ezetimibe treatment on plant sterols and cholesterol metabolism in patients with homozygous sitosterolemia. This study will have important relevance to the health and wellness of Canadians by contributing to an improved understanding of the underlying mechanisms regulating cardiovascular disease development, as well as in the identification of some genetic traits that correlate with various aspects of cholesterol metabolism.