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Dysfunctional Cholesterol: When Good Cholesterol Doesn't Do Its Job

By Pippa Wysong, Access Excellence

CLEVELAND (11/15/04)- Not all HDL (high density lipoprotein), often referred to as "good cholesterol", protects against plaque build-up in artery walls. That's because in some people HDL is dysfunctional, or malformed, and unable to do its job properly, according to researchers from the Cleveland Clinic. The fact that sometimes HDL doesn't do its job helps explain why some people who have high HDL levels still get heart attacks and suffer from other cardiovascular disease, said Stanley Hazen, MD, PhD, head of preventive cardiology and rehabilitation at the Cleveland Clinic.

"Its a bit of a misconception, even among physicians, that having a high HDL completely counteracts having an elevated LDL (low-density lipoprotein) cholesterol level, he said. LDL is often referred to as "bad" cholesterol. While this seems to put a damper on having faith in what cholesterol tests tell you about risk for cardiovascular disease (CVD), all is not lost.

For one, dysfunctional HDL is not that common, plus population studies show that people with high HDL usually have lower risk for heart disease. Still, close to half of people who get heart attacks have healthy cholesterol levels, he said. Now there is also a test under development that one day could be used to help identify people with respectable HDL levels but who may be still at risk, and Dr. Hazen and his research team are the ones working on it. The test will be for a chemical signature showing that a person's HDL is dysfunctional.

Cholesterol is a steroid normally present in the body and is produced by virtually every living cell, especially those in the liver and kidney. It is not all bad and serves several important functions in the body. Cholesterol is an important component of cell membranes and serves as a building block for the production of other steroids and hormones such as testosterone. Some cholesterol is absorbed into the body from dietary sources.

One of the functions of HDL is to carry excess cholesterol from peripheral tissues either onwards to the liver for reuse at another time, or to the bile for excretion. LDL, on the other hand, the major carrier of "bad" cholesterol, helps to deliver cholesterol to various tissues throughout the body where it is used as part of cell membranes during cell growth.

HDL is made of proteins and lipids. Apolipoprotein A-1 (apoA-1) is the main protein component that gives HDL its shape and helps it perform its functions - such as the shuttling of excess cholesterol away from artery walls and preventing plaque build-up. What researchers found is that HDL becomes dysfunctional when an enzyme from white blood cells, called myeloperoxidase (MPO), binds to apoA-1 and modifies it. Once modified, apoA-1 blocks HDL's ability to perform its normal tasks. Normally, MPO helps fight infection and "people with high MPO levels are better at fighting infection," Dr. Hazen said.

A chemical fingerprint for MPO-modified HDL was discovered by the researchers and levels of this marker could be a useful indicator for determining which people with elevated HDL levels may still be at risk for CVD. Likely, it would be a "complimentary test to traditional lipid screening," Dr. Hazen said. However, people should still follow lifestyle advice when it comes to preventing heart disease. Eat smart, exercise and aim for lower LDL levels. "Focus on the basics," he said. The study was published in The Journal of Clinical Investigation.


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