Featured Research

from universities, journals, and other organizations

Gene alteration in mice mimics heart-building effect of exercise

Date:
December 29, 2010
Source:
Dana-Farber Cancer Institute
Summary:
By tweaking a single gene, scientists have mimicked in sedentary mice the heart-strengthening effects of two weeks of endurance training, according to new research. The specific gene manipulation can't be done in humans, they say, but the findings may suggest a future strategy for repairing injured hearts through muscle regeneration.

By tweaking a single gene, scientists have mimicked in sedentary mice the heart-strengthening effects of two weeks of endurance training, according to a report from Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center (BIDMC).

The genetic manipulation spurred the animals' heart muscle cells -- called cardiomyocytes -- to proliferate and grow larger by an amount comparable to normal mice that swam for up to three hours a day, the authors write in the journal Cell.

This specific gene manipulation can't be done in humans, they say, but the findings may suggest a future strategy for repairing injured hearts through muscle regeneration.

"If we learned to manipulate this pathway with specific exercise regimens or with drugs, we might be able to achieve some of the benefits produced by exercise-related heart enlargement," said Bruce Spiegelman, PhD, of Dana-Farber, the study's co-senior author with Anthony Rosenzweig, MD, of BIDMC. Pontus Bostrom, PhD, MD, a postdoctoral fellow at Dana-Farber, is the first author.

The investigators found that the mildly enlarged hearts of the genetically altered mice proved to be surprisingly resistant to a model of cardiac stress that mimics valvular heart disease or the effects of high blood pressure. Someday this observation might lead to therapeutic measures to treat or prevent heart failure, Spiegelman said.

Only recently have scientists discovered that adult cardiomyocytes retain the potential to begin dividing and spawning new muscle cells. In their new publication, the authors describe for the first time a genetic trigger that responds to physical exercise and turns on a molecular pathway that jump-starts cardiomyocyte growth.

"It's well documented that exercise has beneficial effects on metabolism and skeletal muscle, but we hypothesized that it might also have more direct beneficial effects in the heart itself that could be exploited to protect against heart failure," noted Rosenzweig, a cardiologist at BIDMC.

While most previous studies have investigated diseased hearts, these investigators focused their studies on the changes that occur in hearts after endurance exercise. Heart muscle enlargement, or hypertrophy, in response to exercise is popularly known as "athlete's heart" in humans. This process of benign heart muscle growth, the scientists found, involves a distinctly different series of molecular events from those causing pathological hypertrophy -- the enlarged and damaged heart seen in patients suffering from factors like high blood pressure.

While the molecular networks involved in pathological hypertrophy have been studied extensively, there's been little research on the pathways leading to benign heart enlargement, despite the fact that "exercise protects the heart at so many levels," said Bostroom. "We decided to try and find a gene that could be driving some of the important changes we see in exercise."

First, they had adult mice swim daily for increasing amounts of time, and after 14 days found that their hearts were mildly enlarged as a result. Other mice with restricted blood flow in their aorta also showed enlargement, but of the type associated with heart disease. The researchers then screened both sets of animals against a collection of all known transcription factors -- proteins that turn gene activity up or down -- and compared their expression in the two types of heart enlargement.

The key differences turned out to be in a pair of transcription factors acting in concert. One, C/EPB-beta, had reduced activity in the exercised mice while the other, CITED4, was more active.

So, could turning down C/EPB-beta in normal mice cause their hearts to grow as if they had been working out -- even though they did no extra exercise? The answer was yes: Genetic manipulation to reduce C/EPB-beta expression raised the activity of CITED4, and in those mice, cardiomyocytes began dividing and growing in size until their heart muscles resembled those of the endurance swimmers. The mice also had markedly improved maximal exercise capacity even without exercise training.

Importantly, lowering C/EPB-beta expression also protected mice from developing heart failure as a result of restricted aortic blood flow. It is likely that the more-robust cardiomyocytes played an important role in the resistance to heart failure, said the investigators, but they couldn't rule out that other actions of reduced C/EPB-beta and increased CITED4 also contributed.

The authors concluded that developing greater insight into the pathways affecting C/EPB-beta protein expression, or drugs that suppress C/EPB-beta expression in the heart, could be of significant clinical value. "By understanding the pathways that benefit the heart with exercise, we may be able to exploit those for patients who aren't able to exercise," said Rosenzweig. "If there were a way to modulate the same pathway in a beneficial way, it would open up new avenues for treatment."

Other authors are from Dana-Farber, BIDMC, and Brigham and Women's Hospital.

Support for the research was provided in part by the Leducq Foundation Network of Research Excellence and the National Institutes of Health.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Pontus Bostrφm, Nina Mann, Jun Wu, Pablo A. Quintero, Eva R. Plovie, Daniela Panαkovα, Rana K. Gupta, Chunyang Xiao, Calum A. MacRae, Anthony Rosenzweig, Bruce M. Spiegelman. C/EBPβ Controls Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling. Cell, 2010; 143 (7): 1072-1083 DOI: 10.1016/j.cell.2010.11.036

Cite This Page:

Dana-Farber Cancer Institute. "Gene alteration in mice mimics heart-building effect of exercise." ScienceDaily. ScienceDaily, 29 December 2010. <www.sciencedaily.com/releases/2010/12/101223130152.htm>.
Dana-Farber Cancer Institute. (2010, December 29). Gene alteration in mice mimics heart-building effect of exercise. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2010/12/101223130152.htm
Dana-Farber Cancer Institute. "Gene alteration in mice mimics heart-building effect of exercise." ScienceDaily. www.sciencedaily.com/releases/2010/12/101223130152.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 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