Navigation Links
Cholesterol byproduct blocks heart health benefits of estrogen
Date:9/16/2007

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. Mangelsdorf, a Howard Hughes Medical Institute investigator at UT Southwestern. 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.

In normal premenopausal women, the amount of 27HC generated from cholesterol is relatively low compared to the level of estrogen circulating in the blood, leading to enhanced cardiovascular protection. In contrast, when the level of 27HC is higher relative to estrogen, such as during the postmenopausal period or as a consequence of high cholesterol, the researchers speculate that 27HC out-competes estrogen to bind with estrogen receptors, blocking the function of the receptors and resulting in a loss of protection.

This model may help explain why women are better protected than men from cardiovascular disease until they reach menopause, said Dr. Mangelsdorf.

The findings also may help explain why a large clinical trial that evaluated certain hormone replacement therapies (HRT) in postmenopausal women a component of the 15-year Womens Health Initiative had to be halted in 2002 when the hormones appeared to increase a womans risk of heart disease.

In the Womens Health Initiative research program, the women who began taking HRT were an average of 13 years postmenopause, Dr. Manglesdorf said. By the time they started taking this estrogen again, the damage caused by 27HC binding to the estrogen receptors in the cardiovascular system may already have occurred. Once you lose estrogens protection for such an extended period of time, you cant get it back.

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, Dr. Mangelsdorf said. These findings also validate the estrogen receptor as a possible drug target for manufactured SERMs.


'/>"/>

Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert

Related medicine news :

1. Low Cholesterol Linked to Severe Depression and Violent Behavior in Men
2. A better way to measure cholesterol
3. Evening,the best time to take Cholesterol Drug
4. Cholesterol Drugs Prevent Breast Cancer
5. In Search Of A New Drug To Target Cholesterol
6. Testicular cancer linked to high cholesterol
7. Genetics and cholesterol levels
8. Frequent meals can reduce cholesterol
9. Eating More Often May Help Lower Cholesterol
10. Lecithin lowers cholesterol absorption in body
11. Step Aerobics Increases good cholesterol
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... ... in the greater Dallas, Miami, and Raleigh regions, is organizing an extended charity ... a rare and deadly chromosome abnormality. , After struggling since birth with several ...
(Date:10/13/2017)... WI (PRWEB) , ... October 13, 2017 , ... As ... in medicine known as “patient engagement.” The patient is doing more than filling out ... partners. , “There is an increasing emphasis in health care and research on ...
(Date:10/13/2017)... ... ... The American Board of Family Medicine's (ABFM) Board of Directors has selected ... Dr. James C. Puffer upon his retirement. Dr. Newton will serve in the position ... the end of 2018. Upon assuming the role of President and CEO on January ...
(Date:10/13/2017)... ... October 13, 2017 , ... PurhealthRX , a ... utilizing Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD oil will revolutionize the ... a CBD form that can be easily incorporated into liquid products, while reducing costs ...
(Date:10/13/2017)... ... October 13, 2017 , ... Lori R. Somekh, founder ... of ElderCounsel, a national organization of elder law and special needs planning attorneys. “Membership ... rules. It also provides a forum to network with elder law attorneys nationwide,” said ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... -- Hill-Rom Holdings, Inc. (NYSE: HRC), will host its ... on Friday, November 3, 2017, beginning at 7:00 a.m. ... 8:30 a.m. (CDT) / 9:30 a.m. (EDT). ... and guidance for 2018, Hill-Rom executives will also highlight ... and long-range financial outlook through 2020. ...
(Date:9/27/2017)... , Sept. 27, 2017  Commended for their devotion to ... awards. Ranked as number one in the South Florida Business ... in Inc. 5000 yearly list, the national specialty pharmacy has ... Armando Bardisa will soon be honored by SFBJ as ... Set to receive his award in October, ...
(Date:9/25/2017)... --  Montrium , an industry leader in powerful ... Trial Master Files & Inspection Readiness Conference ( ... Services has selected eTMF Connect to ... a leading European contract research organization (CRO), will ... enable greater collaboration with sponsors, improve compliance and ...
Breaking Medicine Technology: