Reverse Cholesterol Transport

The Science of Reverse Cholesterol Transport

Scientists at CV Therapeutics are working to discover potential new therapies that may help increase levels of high-density lipoprotein (HDL), also known as “good cholesterol.” They were among the first to identify a key factor in reverse cholesterol transport: a protein called ABCA1.

Specifically, our scientists found that low levels of ABCA1 can result in an inadequate supply of HDL and subsequent inefficient removal of cholesterol from blood vessel walls. However, stimulating an increase in levels of ABCA1 leads to an increase in HDL, the “good cholesterol” that is most efficient in removing unwanted cholesterol from the body. Cholesterol discarded from cells binds to a newly formed HDL particle that carries it back to the liver for removal from the body. Our researchers accomplished this by performing gene expression analyses in the cells of patients with Tangiers disease who had a defect in cellular cholesterol removal with near-zero levels of HDL. This discovery was recognized by the American Heart Association as one of the top 10 research advances in heart disease and stroke in 1999. View an image series of ABCA1 activity.

Researchers in the reverse cholesterol transport program at CV Therapeutics believe that increasing the activity of the ABCA1 protein to increase supplies of HDL may one day help remove more artery-clogging cholesterol from the body. The goal of our researchers is to discover a new potential agent that may one day help reduce the overall burden of atherosclerosis in patients with coronary artery disease and reduce their lifelong risks for developing heart disease.

While reducing levels of low-density lipoprotein (LDL), or “bad cholesterol,” has been the primary drug target for control of cholesterol for decades, the discovery of this important underlying process may present new opportunities for discovering a novel approach to cholesterol management.