Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Estrogen treatment may help reverse severe pulmonary hypertension

16.09.2011
UCLA researchers have found that the hormone estrogen may help reverse advanced pulmonary hypertension, a rare and serious condition that affects 2 to 3 million individuals in the U.S., mostly women, and can lead to heart failure.

The condition causes a progressive increase in blood pressure in the main pulmonary artery, which originates in the heart's right ventricle and delivers blood to the lungs. The rise in pressure impairs heart function by enlarging the right ventricle, potentially leading to heart failure.

Published in the Sept. 15 issue of the American Journal of Respiratory and Critical Care Medicine, the preclinical study shows that in rats, estrogen treatment can reverse the progression of pulmonary hypertension to heart failure and can restore lung and ventricle structure and function.

The disease progresses slowly, so most patients don't seek treatment until major symptoms occur, such as shortness of breath, dizziness and fainting. According to researchers, current medication for pulmonary hypertension only temporarily reduces the disease's severity. For advanced pulmonary hypertension, there are fewer options, and the condition often necessitates a lung transplant.

"Unfortunately, up until now, there hasn't been an ideal pharmacological therapy to treat advanced pulmonary hypertension," said senior study author Mansoureh Eghbali, Ph.D., an assistant professor of anesthesiology at the David Geffen School of Medicine at UCLA who has a strong background in studying the role of gender and estrogen in cardiovascular diseases. "We hope that this early study may offer insight into new therapies."

The UCLA team found that by treating rats with severe pulmonary hypertension with low doses of estrogen, they were able to prevent the disease from progressing to right-ventricular heart failure; this did not happen in untreated rats.

Systolic blood pressure and ejection fraction — the volume of blood being pumped out of the heart's right chamber with each heart beat — also improved. Tests showed that lung weight, which can increase with the disease and resulting heart-ventricle enlargement, was also corrected. After 10 days of estrogen treatment, function returned to an almost normal state.

The researchers stopped the estrogen therapy after 10 days but continued to observe some of the treated rats. They tracked the continued improvement and found almost full restoration of systolic blood pressure and ejection fraction to normal levels after an additional 12 days.

"We were surprised to find this continued benefit, even after we stopped the estrogen treatment," said the study's first author, Dr. Soban Umar, a UCLA Department of Anesthesiology researcher who has studied pulmonary hypertension and right-ventricular heart failure and is a key member of Eghbali's laboratory team. "These findings suggest that even short-term estrogen therapy may suffice to reverse the disease."

All rats with severe pulmonary hypertension that were treated with estrogen survived by the study's end. Only 25 percent of the untreated rats survived.

The team also explored how estrogen could work in reversing the disease by studying several cellular and molecular mechanisms.

They found that the number of inflammatory cells in rats with pulmonary hypertension increased five-fold, compared with normal rats. In the animals treated with estrogen, this was reversed to normal. The team found that estrogen reduced regulation of a pro-inflammatory gene that also plays a key role in disease development caused by pulmonary hypertension. They also found that estrogen had an inhibitory effect on lung fibrosis.

In addition, the team observed that estrogen therapy restored blood vessels in the lungs and right ventricle whose loss is associated with the disease.

Further study identified that estrogen exerts its biological effects on pulmonary hypertension through a receptor called estrogen receptor beta, a protein that regulates estrogen's activity in the body.

"Estrogen appears to work through an interplay of several factors, including suppression of lung inflammation and fibrosis, as well as reversal of ventricle enlargement," Eghbali said. "We may be able to utilize estrogen receptor beta in the development of future therapies to stimulate estrogen activity to treat pulmonary hypertension."

Researchers had also tested estrogen receptor alpha, the other receptor that controls estrogen activity, but found that it wasn't as effective in treating pulmonary hypertension.

Eghbali added that estrogen receptor beta may prove to be a favorable therapeutic target, since this receptor may require only a short treatment duration and low dosage and has less pro-estrogenic effects on the breasts and uterus than estrogen receptor alpha.

Pulmonary hypertension affects mostly younger women, despite the fact that females in this age group should be under the protective benefits of natural estrogen produced by the body, Eghbali said.

"These patients may have a genetic mutation that is interfering in how estrogen receptor beta directs estrogen activity that is leading to pulmonary hypertension," she said.

Her team's next step is to explore these genetic questions. Currently, Umar and Eghbali are collaborating with UCLA pulmonary hypertension physicians to investigate gender-related issues and to define the role of estrogen in patients with this deadly disease.

The study was funded by the National Institutes of Health.

Additional authors included Andrea Lorga, Humann Matori, Rangarajan Nadadur, Jingyuan Li and Federica Maltese of the department of anesthesiology in the division of molecular medicine at the Geffen School of Medicine, and Arnoud van der Laarse of the department of cardiology at Leiden University Medical Center in the Netherlands.

For more news, visit the UCLA Newsroom and follow us on Twitter.

Rachel Champeau | EurekAlert!
Further information:
http://www.ucla.edu

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>