Cholesterol byproduct blocks heart health benefits o...( DALLAS Sept. 16 2007 New findings ...),Health

DALLAS Sept. 16, 2007 New findings by UT Southwestern Medical Center researchers show that a byproduct of cholesterol metabolism interferes with the beneficial effects estrogen has on the cardiovascular system, providing a better understanding of the interplay between cholesterol and estrogen in heart disease.

The results of the study, available online and in the October issue of the journal Nature Medicine, also may explain why hormone replacement therapy fails to protect some postmenopausal women from heart disease, said Dr. David Mangelsdorf, chairman of pharmacology and senior author of the paper.

The researchers found that in rodents, a molecule called 27-hydroxycholesterol, or 27HC, binds to the same receptors in the blood vessels of the heart to which estrogen binds.

The normal result of this estrogen binding is that blood vessel walls remain elastic and dilated, and damage to the vasculature is repaired, among other heart-protective effects. Other research has shown that postmenopausal women who no longer produce estrogen lose this protective action and become more susceptible to heart disease.

Based on their animal studies and other experiments, the UT Southwestern researchers determined that when estrogen levels dropped relative to the amount of 27HC circulating in the blood, 27HC reacted and bound to the estrogen receptors in the cardiovascular system and blocked their protective function, primarily by inhibiting the production of nitric oxide. Nitric oxide mediates smooth muscle relaxation in blood vessels, aids cell growth and repair, and prevents thrombosis. Reduced levels of nitric oxide in blood vessels has been linked with high cholesterol and diabetes.

In animals fed a high-fat, high-cholesterol diet, both cholesterol and 27HC levels were elevated.

We found that 27HC can effectively inhibit estrogen function in vascular tissue by binding to estrogen receptors, said Dr. Mangel
'/>"/>