The physiological role of P-glycoprotein in the gastrointestinal absorption of cholesterol

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among Canadians, accounting for an estimated 36 per cent of premature deaths. The majority of these CVD-related deaths result from ischemic heart disease (insufficient blood supply to the heart), which is often caused by plaque building up on the inside of blood vessels (atherosclerosis). As tobacco use has declined, elevated low-density lipoprotein (LDL) cholesterol levels have emerged as the major risk factor for the development of atherosclerosis. Treatment of elevated cholesterol has traditionally involved a drug regime of blood cholesterol-reducing statins, coupled with diet and lifestyle changes. However, increasing research evidence is driving health agencies to further lower their recommended target levels for low-density lipoprotein (LDL) cholesterol. These reduced levels may not be achievable with traditional interventions, requiring the development of new combination therapies. Inhibiting the absorption of cholesterol from the gastrointestinal tract is an attractive target for combination therapy with statins. Stephen Lee is investigating a transporter protein that is produced in the intestinal tract during the process of cholesterol absorption and processing. While several preliminary studies have implicated this protein in the cholesterol absorption process, none have investigated how this process is affected by diet. Stephen will examine the role of the protein on the absorption of cholesterol among mice fed one of four specific diets with precise fat and cholesterol contents. The proposed research may lead to the discovery of a new pharmacological target for future therapies that work with statin treatments to reduce cholesterol levels.