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 31, 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 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
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