Navigation Links
Gladstone scientists identify genetic mechanism linked to congenital heart disease
Date:1/22/2012

SAN FRANCISCO, CAJanuary 22, 2012Scientists at the Gladstone Institutes have identified a finely tuned mechanism by which fetal heart muscle develops into a healthy and fully formed beating heartoffering new insight into the genetic causes of congenital heart disease and opening the door to one day developing therapies to fight this chronic and potentially fatal disorder.

In a paper being published online today in Nature Genetics, researchers in the laboratory of Gladstone Senior Investigator Benoit Bruneau, PhD, describe the roles that two genesEzh2 and Six1play in embryonic heart development, while also uncovering how the genetic basis of embryonic heart formation can have profound health consequences later in life.

This research highlights the emerging importance of a biological process called "epigenetics," in which a genetic change that is inherited by a cell or organism early during development has long-term consequences. Epigenetics is of particular interest in heart development, as the incorrect activation of genes in fetal development can lead to congenital heart disease into adulthood.

"Approximately 1.3 million children and adults in the United States live with congenital heart diseaserequiring daily medications, surgeries and for some, heart transplants," said Dr. Bruneau, who is also a professor of Pediatrics at the University of California, San Francisco, with which Gladstone is affiliated. "An understanding of the epigenetic regulation of heart development could someday bring us closer to improving the lives of these individuals."

At specific times during healthy heart development, Ezh2 acts as a "master regulator," shutting off genes that are no longer needed or that need to be kept off. In the past, the focus has been on which genes get switched on during normal heart development. But in this paper, Dr. Bruneau, along with Gladstone Postdoctoral Scholar Paul Delgado-Olguin, PhD, investigated which genes must remain off to ensure the development of a healthy heart.

In laboratory experiments, Drs. Bruneau and Delgado-Olguin removed Ezh2 from mice at various developmental stages, monitoring any ensuing genetic or physical changes and comparing them to mice whose Ezh2 remained intact. Surprisingly, mice without Ezh2 developed normally in the uterus. It wasn't until after birth that they began to show problems. Their hearts became enlarged and weakened and were unable to pump blood efficiently. An enlarged heart is a hallmark feature of cardiomyopathy, a form of congenital heart disease that afflicts thousands of children each year and for which the only manifestation may be sudden death.

Further analysis revealed that Six1 is normally on only for a brief period during heart development, after which Ezh2 shuts it off for good. But without Ezh2 to act as a regulator, Six1 remains onleading to heart problems later in life.

"When Six1 remains active for too long in Ezh2-deficient mice, it boosts the activity of other genes that shouldn't be activated in heart-muscle cellssuch as genes that make skeletal muscle," said Dr. Delgado-Olguin. "The enlargement and thickening of the mice's hearts over time eventually led to heart failure."

This breakthrough may help researchers improve their understanding of the genetic causes of congenital heart disease while also pointing the way to potential therapies. For example, a type of congenital heart disease called dilated cardiomyopathy is caused by mutations in Eya4, a gene that is also regulated by Ezh2 in the heart.

"Six1 is just one of many Ezh2-regulated genes that are vital for heart development," said Dr. Bruneau. "Our next goal is to find out exactly how Ezh2 regulates these other genes, so that we can begin to develop a complete genomic blueprint of how a heart becomes a heart."


'/>"/>

Contact: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534
Gladstone Institutes
Source:Eurekalert  

Related medicine news :

1. Gladstone scientists identify gene critical for cell responses to oxygen deprivation
2. Gladstone and Lundbeck collaborate to study neurovascular disease
3. Gladstones Deepak Srivastava elected to the American Academy of Arts and Sciences
4. Gladstones Robert Mahley to receive Research!America advocacy award
5. Scientists Agree to Delay Controversial Bird Flu Research
6. Scientists shed new light on link between killer cells and diabetes
7. NIH scientists identify novel approach to view inner workings of viruses
8. UNC scientists collaborate to find first major genetic mutation associated with hereditary prostate cancer risk
9. Scientists Identify Inherited Prostate Cancer Gene
10. Scientists Create First Monkeys With Mixed Genomes
11. Scientists reassess weight loss surgery for type 2 diabetes
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Gladstone scientists identify genetic mechanism linked to congenital heart disease
(Date:5/4/2016)... ... May 04, 2016 , ... Fertility Centers of New England announced ... Their new Maine Fertility Center provides convenient access to care for patients seeking fertility ... staff at Women’s Wellness Comprehensive Care in Portland,” said Fertility Centers of New England ...
(Date:5/4/2016)... , ... May 04, 2016 , ... ... certified that their Vasont Universal Integrator (VUI) extension supports the latest release of ... of Adobe FrameMaker 2015 interlace the process of creating, editing and storing XML. ...
(Date:5/3/2016)... Minnesota (PRWEB) , ... May 04, 2016 , ... ... more than 40 national and global construction firms representing the Construction Industry Safety ... have joined forces with one purpose: to inspire everyone in the industry to ...
(Date:5/3/2016)... ... May 04, 2016 , ... The National Association of ... its VIP Woman of the Year Circle. She is recognized with this prestigious distinction ... women, boasting more than 850,000 members and over 200 operating Local Chapters. , “I’m ...
(Date:5/3/2016)... ... May 03, 2016 , ... According to an ... with numerous issues related to medical care in the hospital setting, which include ... manner from hospital staff. Commenting on this article, the founder of House Call ...
Breaking Medicine News(10 mins):
(Date:5/3/2016)... , May 3, 2016 ... bekannt, dass sie einen entscheidenden Meilenstein durch ... Ein Aufruf zum Handeln, um Patientenresultate  bei ... trägt zu Fortschritten im Verständnis der Hepatischen ... ein Bewusstsein für Hepatische Enzephalopathie in der ...
(Date:5/2/2016)... , May 2, 2016  Celsion Corporation (NASDAQ: ... company, today announced data from the first cohort ... clinical trial (the OVATION Study) combining GEN-1, the ... for the treatment of newly-diagnosed patients with advanced ... by interval debulking surgery.  In the first three ...
(Date:4/29/2016)... , April 29, 2016 ... Directeur Financier Sanofi, leader ... publie ses résultats pour le premier ... Groupe, Jérôme Contamine, commente les résultats ... les perspectives pour le reste de ...
Breaking Medicine Technology: