Featured Research

from universities, journals, and other organizations

Pulmonary Arterial Hypertension Reversed In Mouse Models

Date:
October 26, 2009
Source:
University of California - San Diego
Summary:
Researchers have identified a key protein that promotes the development of pulmonary arterial hypertension in humans and mice. This groundbreaking discovery has implications for future drug therapies that may extend the life of patients with pulmonary arterial hypertension and prevent the need for lung transplantation, currently the only cure for this debilitating disease.

Researchers at the University of California, San Diego, have identified a key protein that promotes the development of pulmonary arterial hypertension in humans and mice. This groundbreaking discovery has implications for future drug therapies that may extend the life of patients with pulmonary arterial hypertension and prevent the need for lung transplantation, currently the only cure for this debilitating disease.

In a paper to be published online in Nature Medicine on October 25, Patricia Thistlethwaite, MD, PhD, Professor of Surgery and cardiothoracic surgeon in UCSD's Department of Surgery, and colleagues describe the genetic pathway by which vascular smooth muscle cells associated with pulmonary arterial hypertension are switched on to proliferate by a receptor protein called Notch-3. With this finding, the researchers were able to block and reverse the pathway of disease in mice.

"The UCSD team found that pulmonary hypertension is characterized by overexpression of Notch-3 and that the severity of the disease correlates with the amount of this protein in the lung," said Thistelthwaite. "We showed that a mouse model lacking this protein does not develop pulmonary hypertension, and in addition, that the disease can be effectively treated with an enzyme called γ-secretase inhibitor, which blocks Notch-3 activation."

In Thistlethwaite's laboratory, mice with pulmonary arterial hypertension that were treated with the γ-secretase inhibitor showed reversal of the disease. Forms of this drug are currently in use in Phase 1 trials for the treatment of Alzheimer's disease.

Pulmonary arterial hypertension is a form of high blood pressure in the lung's arteries. The disease begins when tiny arteries in the lungs become narrow, blocked or destroyed causing resistance to blood to flow. As the pressure builds, the heart's lower right chamber becomes overworked and weakens, leading to ventricular failure. The condition afflicts more than 100,000 patients in the United States, causing 20,000 deaths per year.

"Pulmonary arterial hypertension is more common in the human population than is currently realized, and unfortunately, is often fatal," said co-author Stuart Jamieson, MB, FRCS, Distinguished Professor of Surgery and Chair of Cardiothoracic Surgery at UC San Diego Medical Center. "Current drugs to treat pulmonary arterial hypertension focus on dilating the arterial vessels but do not address the eventual thickening of the artery walls. Fortunately, by identifying this drug target it seems we are now on the right path to developing an intervention that prevents abnormal cell proliferation."

Additional contributors to the paper from UC San Diego Health Sciences are first author Xiaodong Li, Xiaoxue Zhang, Robin Leathers, Ayako Makino, Chengqun Huang, Pouria Parsa, Jesus Macias, Jason X-J Yuan, Stuart W. Jamieson, and Patricia A. Thistlethwaite. The research was supported by a grant from the National Institutes of Health.


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University of California - San Diego. "Pulmonary Arterial Hypertension Reversed In Mouse Models." ScienceDaily. ScienceDaily, 26 October 2009. <www.sciencedaily.com/releases/2009/10/091025162528.htm>.
University of California - San Diego. (2009, October 26). Pulmonary Arterial Hypertension Reversed In Mouse Models. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2009/10/091025162528.htm
University of California - San Diego. "Pulmonary Arterial Hypertension Reversed In Mouse Models." ScienceDaily. www.sciencedaily.com/releases/2009/10/091025162528.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins