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Cholesterol breakthrough
New find could lead to better drugs, therapies

By Melissa Erickson
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The medical community has known for a long time that high levels of cholesterol in the blood lead to a higher risk of coronary artery disease and, in turn, heart attacks. What hasn’t been known is how “bad” cholesterol enters the artery walls — until now.

Researchers at UT Southwestern revealed for the first time how a protein called SR-B1 ferries low-density lipoprotein, or LDL, cholesterol into and across the cell walls of blood vessels. This process causes plaque to build up and narrow the blood vessels, which can lead to heart attack and stroke. The study also found a second protein called DOCK4 that partners with SR-B1 and is necessary for the process.

Cardiovascular disease is the No. 1 cause of death worldwide, and coronary artery disease, which underlies heart attacks and strokes, accounts for over 60 percent of cardiovascular deaths in the United States, according to the American Heart Association.

Figuring out how LDL enters the artery wall was much like solving a mystery, said Dr. Philip Shaul, senior author of the study published in April online in Nature. Previously, many scientists assumed that LDL entered artery walls through damaged or disrupted endothelial cells, the artery wall’s protective barrier, said Shaul, director of the Center for Pulmonary and Vascular Biology at UT Southwestern Medical Center in Dallas.

The discovery may lead to a whole new class of drug or gene therapies that could inhibit or silence the offending SR-B1 and DOCK4 proteins in the endothelial cells in order to prevent atherosclerosis, or the hardening of the arteries, Shaul said.

What is cholesterol?

Our bodies need a small amount of cholesterol to function properly, but too much is unhealthy. A waxy, fat-like substance made by the liver, cholesterol is found in all the cells of the body. It’s also in fatty meats like bacon, dairy products such as butter, cheese and whole milk, and foods made with transfat including cookies and crackers, fast food and frozen pizza.

How is it measured?

A blood test called a lipoprotein panel measures cholesterol levels including total cholesterol, LDL and HDL (high-density lipoprotein, or “good” cholesterol) and triglycerides, which are another form of fat found in the blood. Cholesterol is measured in milligrams per deciliter. The test also measures non-HDL, which is the total cholesterol minus HDL cholesterol.

What’s healthy?

Normal cholesterol guidelines vary from source to source, but these from the National Heart, Lung and Blood Institute are easy to understand, Shaul said.

For men 20+

Total cholesterol
125 to 200mg/dL
Non-HDL
Less than 130mg/dL
LDL
Less than 100mg/dL
HDL
40mg/dL or higher

For women 20+

Total cholesterol
125 to 200mg/dL
Non-HDL
Less than 130mg/dL
LDL
Less than 100mg/dL
HDL
50mg/dL or higher

Lowering your cholesterol

In addition to paying attention to traditional risk factors such as such as smoking, high blood pressure and high blood sugar, those wanting to lower cholesterol should also consider family history and ethnicity.

The first step of prevention is a healthy lifestyle, including a heart-healthy diet and regular exercise, with the use of medications (primarily statins) to lower cholesterol in individuals who are at higher risk for cardiovascular disease, said Dr. Chiadi Ndumele, assistant professor of medicine at Johns Hopkins
Medicine.