Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCSD Researchers Identify Gene Pathway Causing Pulmonary Hypertension

06.02.2003


Researchers at the University of California, San Diego (UCSD) School of Medicine have identified an over-active gene and the molecular events it triggers to cause acquired cases of pulmonary hypertension, a form of high blood pressure in the lungs that kills about one percent of the population each year.



The findings, published in the February 6, 2003 issue of the New England Journal of Medicine, offer the first specific molecular targets for development of new therapies.

"Although a small subset of patients benefit from surgery to remove blood clots from the lungs, currently the only treatment for most types of pulmonary hypertension is lung transplantation," said the study’s senior author Patricia Thistlethwaite, M.D., Ph.D., an assistant professor in the UCSD Division of Cardiothoracic Surgery.


The researchers found that a gene called angiopoietin-1, which is normally involved in smooth-muscle growth in newly developing embryonic blood vessels, somehow gets inappropriately turned on in adulthood. As angiopoietin-1 aberrantly over-expresses itself, it initiates a molecular chain of events that causes muscle cell proliferation within the lining of the lung’s blood vessels. As the vessel wall thickness grows, the small lung arteries become progressively narrowed and blocked.

Almost all patients with pulmonary hypertension acquire the disease from diverse causes such as congenital heart defects, autoimmune disease, left-sided heart failure, blood clots in the lungs, drug interactions or vascular diseases. A handful of patients inherit a rare form of the disease from a mutation in a gene called bone morphogenetic protein receptor type2 (BMPR2).

"We wondered whether a common molecular mechanism underlies all the different causes of pulmonary hypertension as well as the inherited form," Thistlethwaite said.

The investigators reasoned that since angiopoietin-1 was involved in embryonic smooth-muscle development, an aberrant turn-on of this gene might cause the over-growth of muscle tissue in adults. During an 18 month period, the team obtained lung biopsies from 42 pulmonary hypertension patients who had acquired pulmonary hypertension from a variety of causes. For comparative purposes, they also obtained biopsies from 19 individuals without pulmonary hypertension, who were undergoing lung surgery.

Using sophisticated laboratory tests on the lung tissue, the scientists found that angiopoietin-1 attached itself to a receptor (or docking protein) called TIE2, which is only located in the lining of blood vessels. In turn, the angiopoietin-1/TIE2 duo caused the down-regulation, or work slow-down, of another gene called bone morphogenetic protein receptor type1 (BMPR1). The result was the muscle build-up characteristic of pulmonary hypertension.

"Researchers have known for years that BMPR1 and BMPR2 work together on the cell surface to stimulate intracellular signaling," said Thistlethwaite. "This means that our findings show a link between the inherited form of pulmonary hypertension, caused by a BMPR2 mutation, and the non-familial, acquired form, caused by the angiopoietin-1, TIE2, BMPR1 molecular pathway."

Currently, the Thistlethwaite team is working on potential inhibitors of angiopoitin-1, to see if they can stop pulmonary hypertension in rodent models.

The study was funded by the Charles B. Wang Foundation and grants from the National Institutes of Health. Additional authors of the paper were Lingling Du, M.D.; Christopher C. Sullivan, M.S.; Danny Chu, M.D.; Augustine J. Cho, B.A.; Masakuni Kido, M.D., and Stuart W. Jamieson, M.D., FRCS, UCSD Division of Cardiothoracic Surgery; Paul L. Wolf, M.D., UCSD and the San Diego VA Healthcare System; Jason X.-J. Yuan, M.D., Ph.D., UCSD Pulmonary and Critical Care Medicine; and Renna Duetsch, Ph.D., UCSD Biostatistics.


News media contact:
Sue Pondrom
619-543-6163
spondrom@ucsd.edu

Sue Pondrom | EurekAlert!
Further information:
http://health.ucsd.edu/news/
http://health.ucsd.edu/news/2003/02_05_Thistle.html
http://www.ucsd.edu/

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>