Navigation Links
Rescuing injured hearts by enhancing regeneration

Using a two-drug approach, researchers at Children's Hospital Boston have demonstrated that it may be possible to rescue heart function after a heart attack and protect the heart from scarring. Working with rats, they combined an agent that overcomes a natural inhibitor of cell division with a naturally occurring growth factor that encourages blood vessel growth (angiogenesis). Together, these two agents enabled heart-muscle cells to multiply and the heart to regain its function after a simulated myocardial infarction. The study will appear in the October 17 issue of the Proceedings of the National Academy of Sciences (posted online during the week of October 9).

Normally, after a heart attack, the damaged heart muscle cannot grow back and is instead replaced by scar tissue. Excessive scarring can impair the heart's pumping capacity and can lead to life-threatening arrhythmias. Heart-muscle cells (cardiomyocytes) normally cannot replicate in mammals, a major obstacle to regeneration. However, in a paper last year, Felix Engel, PhD, and Mark Keating, MD, in the Department of Cardiology at Children's Hospital Boston, showed that they could coax cardiomyocytes to multiply in a petri dish by inhibiting an enzyme known as p38 MAP kinase, which normally suppresses cardiomyocyte replication. [See: www.childrenshospital.org/newsroom/Site1339/mainpageS1339P1sublevel139.html]

Engel and Keating (Keating is now at the Novartis Institute for BioMedical Research) now build on this finding. They studied 120 rats, some with simulated heart attacks. After the injury, the animals were randomly assigned to receive injections with a p38 MAP kinase inhibitor alone, the angiogenesis stimulator FGF1 alone, both agents together, or saline (placebo) for four weeks. Three months later, rats that had received both FGF1 and the p38 MAP kinase inhibitor had markedly improved heart function, as measured on echocardiograms: their hearts pumped almost as well as the hearts of uninjured rats. They also had reduced thinning of the cardiac wall and the least amount of scarring.

Rats receiving only the p38 MAP kinase inhibitor had increased proliferation of cardiomyocytes, but no longer had improved heart function at three months. Those receiving only FGF1 maintained their functional improvement, but did not show as much cell proliferation as those receiving the p38 MAP kinase inhibitor. Rats receiving both agents had the greatest improvements in both cell proliferation and heart function.

The findings suggest that getting cardiomyocytes to replicate is not enough to rescue heart function, but that angiogenesis is also needed, Engel says.

"Regeneration is not just making more cardiomyocytes," he says. "Cardiomyocytes need a blood supply and oxygen to survive. FGF1 did not have a great effect on cell proliferation, but we found it was providing a new blood supply. If you just inhibit p38 MAP kinase, you don't get blood vessels."

Two important steps are needed to turn these findings into a treatment, Engel says. First is to show that the treatment works when not given immediately after the heart attack, since many people sustain progressive damage to their hearts from repeated minor infarctions. In this study, rats were treated soon after injury.

Second is the need to develop a safe delivery method. Because FGF1 stimulates angiogenesis, it has the potential for serious side effects if it goes to places other than the heart, possibly promoting tumor growth, for example. And the p38 MAP kinase inhibitor has been shown to damage the liver.

"Every treatment trying to induce proliferation of cardiomyocytes also carries a risk of inducing tumor growth, and thus you have to limit the time and location of treatment," Engel adds.

One possibility is to inject smaller doses of the agen ts into the damaged area of the heart in gel form, or instill them through a catheter, so that they would remain in the heart and be released slowly over time. Engel and colleagues recently reported another compound that stimulates cardiomyocyte proliferation (Chemistry and Biology, Sept. 2006), and others are under investigation.

"In the end, we'd like a treatment that could be given systemically," Engel says.
'"/>

Source:Children's Hospital Boston


Related biology news :

1. Molecular messengers perform a crucial role in the ability of injured nerve cells to heal themselves
2. NASA technology helping injured US troops
3. Bone marrow stem cells may heal hearts even years after heart attacks
4. Mice with glowing hearts shed light on how hearts develop
5. Free-radical busting antioxidants might not promote healthy hearts
6. UT Southwestern researchers find gene mutation that leads to broken hearts
7. Adult stem cell research at UB targets damaged hearts
8. Newts which regrow their hearts
9. Mechanical artificial hearts can remove need for heart transplant by returning heart to normal
10. Mutation improves memory, may lead to memory-enhancing pill
11. Researchers feed tiny pills of RNA to planarians to identify genes essential for regeneration

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/15/2016)... -- A new partnership announced today will help life ... a fraction of the time it takes today, ... insurance policies to consumers without requiring inconvenient and ... rapid testing (A1C, Cotinine and HIV) and higi,s ... pulse, BMI, and activity data) available at local ...
(Date:4/14/2016)... BioCatch ™, the global ... the appointment of Eyal Goldwerger as CEO. ... Goldwerger,s leadership appointment comes at a time of significant ... of its platform at several of the world,s largest ... unique cognitive and physiological factors, is a winner of ...
(Date:3/31/2016)... March 31, 2016   ... or the "Company") LegacyXChange is excited to ... its soon to be launched online site for trading ... ) will also provide potential shareholders a sense ... technology to an industry that is notorious for fraud. ...
Breaking Biology News(10 mins):
(Date:4/27/2016)... ... April 27, 2016 , ... Most consumers ... with fingerprint recognition for secure access, voice recognition for hands-free communication, and facial ... are interacting with biometrics technology today. But if they asked Joey Pritikin, ...
(Date:4/27/2016)... ... April 27, 2016 , ... The Board of ... appointment of John Tilton as Chief Commercial Officer.  Mr. Tilton joined Biohaven from ... founding commercial leaders responsible for the commercialization of multiple orphan drug indications. ...
(Date:4/27/2016)... ... April 27, 2016 , ... A compact PET scanner ... and MRI (Magnetic Resonance Imaging) in existing third-party MRI systems. PET and MRI ... small animal subjects. Simultaneous PET/MRI imaging offers a solution to many challenges that ...
(Date:4/27/2016)... -- MedDay, a biotechnology company focused on the ... Catherine Moukheibir as Chairman of its Board of Directors. ... Garaud , who contributed to the rapid development of the ... Catherine started her career in strategy consulting and investment banking ... .  She held C-Suite level roles in some of ...
Breaking Biology Technology: