Hyperlipidemia—also known as Tangier Disease—is characterized by very high levels of cholesterol, lipids, and lipid-related proteins in the blood. There are several different types of hyperlipidemia, some of which are life-threatening and have a strong genetic component.
One example is familial hypercholesterolemia, a severe and genetically-linked form of hyperlipidemia that affects at least one in 500 individuals. If not properly diagnosed and treated from a very young age, individuals with hypercholesterolemia can have blood-borne cholesterol levels that are over three times higher than normal. By their late teens, untreated hypercholesteremic individuals often succumb to a severe form of atherosclerosis, followed by premature death in a few short years.
One strategy to counteract the devastating atherosclerotic effects of high cholesterol is to increase the body's supply of high density lipoproteins—also known as HDL or the "good cholesterol"—to remove cholesterol from the bloodstream and lower the risk of cardiovascular disease.
By studying ABCA1, a gene absolutely critical for the production of HDL in humans that was discovered here at the CMMT, we aim to find ways to increase the body's production of HDL and reduce the atherosclerotic effects of hyperlipidemia. Using a novel technology termed conditional gene targeting, we work to understand the major sites of HDL production in the body, and how ABCA1 in these tissues affects the development of atherosclerosis. This information is absolutely crucial for the design of novel therapies that would raise the levels of ABCA1 activity is specific parts of the body to protect against the devastating consequences of hyperlipidemia.
This work will generate important new knowledge about HDL production, risk for atherosclerosis in hyperlipidemia sufferers and ABCA1 function in specific cell types. By understanding how ABCA1 functions in different parts of the body, and how it responds to various environmental and genetic stimuli we will be in a position to design lifestyle and pharmacological therapeutic options for the prevention and treatment of this leading cause of death.
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Brunham LR, Kruit JK, Pape TD, Parks JS, Kuipers F, Hayden MR. Tissue-specific induction of intestinal ABCA1 expression with a liver X receptor agonist raises plasma HDL cholesterol levels. Circ. Res. 99(7):672-4. (2006) PMID 16946132
Singaraja RR, Van Eck M, Bissada N, Zimetti F, Collins HL, Hildebrand RB, Hayden A, Brunham LR, Kang MH, Fruchart JC, Van Berkel TJ, Parks JS, Staels B, Rothblat GH, Fiévet C, Hayden MR. Both hepatic and extrahepatic ABCA1 have discrete and essential functions in the maintenance of plasma high-density lipoprotein cholesterol levels in vivo. Circulation 114(12):1301-9. (2006) PMID 16940190