Sept 17 : Researchers at the UT Southwestern Medical Center have found that a byproduct of cholesterol metabolism blocks the health benefits of estrogen.

The finding, the researchers state, provides a better understanding of the relationship between cholesterol and estrogen, the primary female sex hormone, in heart disease.

It may also, says lead researcher Dr. David Mangelsdorf, chairman of pharmacology, shed light on why hormone replacement therapy fails to protect some postmenopausal women from heart disease.

The researchers carried out their study in mice, and noted that 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 is that blood vessel walls remain elastic and dilated, and damage to the vasculature is repaired, among other heart-protective effects.

However earlier studies have shown that postmenopausal women – who no longer produce estrogen – lose this protective action and become more susceptible to heart disease.

Based on their study, the researchers found that when estrogen levels drops relative to the amount of 27HC circulating in the blood, 27HC reacts and binds to the estrogen receptors in the cardiovascular system and blocks 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.

“We found that 27HC can effectively inhibit estrogen function in vascular tissue by binding to estrogen receptors,” Nature quoted Dr. Mangelsdorf, a Howard Hughes Medical Institute investigator at UT Southwestern, as saying.

“This study not only illustrates the damaging effects high cholesterol has on the heart but also supports the notion that the relative levels of 27HC and estrogen in the vasculature are contributing factors to the risk for cardiovascular disease.

“This model may help explain why women are better protected than men from cardiovascular disease until they reach menopause”.

The researchers also found that 27HC works predominantly on estrogen receptors in the cardiovascular system. When it binds to estrogen receptors in other tissues, such as reproductive tissues, it has no effect on their reproduction-related functions.

This property of 27HC makes it a “selective estrogen receptor modulator,” or SERM, the first such naturally occurring molecule known to exhibit such selectivity.

“This molecule is remarkable in its selectivity for the vasculature. These findings also validate the estrogen receptor as a possible drug target for manufactured SERMs,” Dr Mangelsdorf said.

The study is available online and in the October issue of the journal Nature Medicine. (ANI)

Tags:Heart-disease