Jay Heinecke/HDL composition

Why Bad Things Can Happen To The Heart When 'Good' Cholesterol Goes
Bad

Science Daily - It's yet another example of how a good thing can go
bad: Researchers have found evidence in laboratory studies that 'good'
cholesterol, renowned for its ability to protect against heart
disease, can undergo detrimental changes in protein composition that
make it 'bad' for the heart.

Scientists long have suspected that there may be dysfunctional forms
of so-called 'good' cholesterol, also called high density lipoprotein
(HDL) cholesterol, that can lose their heart-protective effect. But
the exact chemical composition of HDL, both good forms and bad, has
remained largely unknown, researchers say.

In a study recently presented at the 234th national meeting of the
American Chemical Society, researchers reported what is believed to be
the most detailed analysis to date of the protein composition of HDL.
They uncovered surprising new information about HDL, including
previously unrecognized proteins that appear to play an important role
in maintaining heart health. Their findings could one day lead to new,
more accurate lab tests for heart disease as well as new, potentially
life-saving treatments for the disease, which is the number one killer
in the United States and other developed countries.

"Targeting HDL could represent a new horizon in heart disease
diagnosis and treatment," says study leader Jay Heinecke, M.D., of the
University of Washington School of Medicine in Seattle. "But simply
boosting HDL levels may not be enough to prevent heart disease. You
might have to target the right proteins in HDL."

To further explore HDL's role in the body, Heinecke and colleagues
conducted a detailed analysis of the protein composition of HDL and
found 48 proteins, including 22 proteins that play a role in
cholesterol metabolism and 13 proteins not previously known to exist
in HDL.

Of the proteins identified in HDL, some might play a previously
unsuspected role in preventing atherosclerotic plaques from rupturing.
The rupture of these plaques, followed by formation of an artery-
plugging blood clot, causes most heart attacks, the researcher says.
Other important protective proteins identified in HDL may protect
heart cells from injury during a heart attack, Heinecke says.

But other components found in HDL have potentially destructive effects
in the body by promoting cholesterol accumulation and inhibiting some
of the heart-protective effects of other proteins, Heinecke says.
Thus, boosting HDL cholesterol levels alone might not protect the
heart, he says. Indeed, a major pharmaceutical company recently
withdrew an experimental HDL-boosting drug when it was found that the
drug caused an increase in deaths and heart problems, Heinecke notes.

A better understanding of the protein components of HDL could
therefore lead to new, more accurate tests for predicting or
evaluating heart disease, says Heinecke, whose study is funded by the
National Institutes of Health. He notes that heart attacks can occur
in people whose cholesterol levels appear normal and that conventional
diagnostic tests for cholesterol levels do not always give a clear
picture of the disease. More effective, targeted HDL-based
interventions could potentially save lives, especially when used in
combination with statin drugs that target low density lipoproteins
(LDL), or bad cholesterol, says Heinecke, who notes that more studies
are needed.

"There's still a lot we don't know about heart disease," Heinecke
says. "HDL is still a big mystery, but we're closing in on it and
we're pretty excited."

Note: This story has been adapted from a news release issued by
American Chemical Society.

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