Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find protein 'switch' central to heart cell division

04.03.2014

Discovery advances efforts to replace damaged heart muscle

In a study that began in a pair of infant siblings with a rare heart defect, Johns Hopkins researchers say they have identified a key molecular switch that regulates heart cell division and normally turns the process off around the time of birth. Their research, they report, could advance efforts to turn the process back on and regenerate heart tissue damaged by heart attacks or disease.

Heart Muscle Cell

In the heart muscle cell above, the arrows show an early sign of replication.

Credit: Johns Hopkins Medicine

"This study offers hope that we can someday find a way to restore the ability of heart cells to divide in response to injury and to help patients recover from many kinds of cardiac dysfunction," says cardiologist Daniel P. Judge, M.D., director of the Johns Hopkins Heart and Vascular Institute's Center for Inherited Heart Diseases. "Things usually heal up well in many parts of the body through cell division, except in the heart and the brain. Although other work has generated a lot of excitement about the possibility of treatment with stem cells, our research offers an entirely different direction to pursue in finding ways to repair a damaged heart."

Unlike most other cells in the body that regularly die off and regenerate, heart cells rarely divide after birth. When those cells are damaged by heart attack, infection or other means, the injury is irreparable.

Judge's new findings, reported online March 4 in the journal Nature Communications, emerged from insights into a genetic mutation that appears responsible for allowing cells to continue replicating in the heart in very rare cases.

The discovery, Judge says, began with the tale of two infants, siblings born years apart but each diagnosed in their earliest weeks with heart failure. One underwent a heart transplant at three months of age; the other at five months. When pathologists examined their damaged hearts after they were removed, they were intrigued to find that the babies' heart cells continued to divide — a process that wasn't supposed to happen at their ages.

The researchers then hunted for genetic abnormalities that might account for the phenomenon by scanning the small percent of their entire genome responsible for coding proteins. One stood out: ALMS1, in which each of the affected children had two abnormal copies.

The Johns Hopkins researchers also contacted colleagues at The Hospital for Sick Children in Toronto, Canada, who had found the same heart cell proliferation in five of its infant patients, including two sets of siblings. Genetic analysis showed those children had mutations in the same ALMS1 gene, which appears to cause a deficiency in the Alström protein that impairs the ability of heart cells to stop dividing on schedule. The runaway division may be responsible for the devastating heart damage in all of the infants, Judge says.

These mutations, it turned out, were also linked to a known rare recessive disorder called Alström syndrome, a condition associated with obesity, diabetes, blindness, hearing loss and heart disease.

In further experiments, the Johns Hopkins researchers cultured mouse heart cells, then turned off the ALMS1 gene. Compared to those with normal ALMS1 genes, the number of heart cells in samples without this gene increased by an additional 10 percent. The researchers then contacted colleagues at Jackson Laboratory in Maine who had genetically engineered and bred mice with an ALMS1 mutation. They found that the animals with the mutation had increased proliferation of heart cells after two weeks of age, compared to mice with a normal version of the ALMS1 gene. The cell proliferation did eventually stop in the mice, says Judge, an associate professor at the Johns Hopkins University School of Medicine.

Judge says precise knowledge of the regulatory role played by the ALMS1 mutation should advance the search for ways to help regenerate heart muscle tissue in a controlled fashion. Much work in the field of regeneration has been focused on the use of stem cells, which have the remarkable potential to develop into many different cell types.

Judge cautions that efforts to manipulate ALMS1 to repair damage would be tricky, because uncontrolled proliferation may lead to serious and even lethal complications.

"The children who helped us recognize the importance of this gene were born with a rare condition that leads to heart failure and many other problems, such as diabetes, obesity, blindness and deafness," he says. "Now we hope to apply these discoveries to help millions of others with heart disease."

###

This research was supported by funding from the JHU Friends in Red; the Zegar Family Foundation; the Michel Mirowski, M.D. Discovery Fund; Mrs. Seena Lubcher; the National Institutes of Health's National Heart, Lung and Blood Institute (4R00HL09223) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD036878); the American Heart Association's Beginning Grant-in-Aid; and the Lundbeck Foundation. The Johns Hopkins University Center for Inherited Disease Research is supported by funding from NIH contract HHSN268200782096C.

Other Johns Hopkins researchers involved in the study include Lincoln T. Shenje, M.D., Ph.D.; Peter Andersen, Ph.D.; Marc K. Halushka, M.D., Ph.D.; Cecillia Lui; Laviel Fernandez; Nuria Amat-Alarcon, M.S.; Raluca Yonescu, M.D.; Denise A. S. Batista, Ph.D.; Yan Chen; Stephen Chelko, Ph.D.; Jane Crosson, M.D.; Janet Scheel, M.D.; Luca Vricella, M.D.; Brain D. Craig; Beth A. Marosy, M.S.; David W. Mohr; Kurt Hetrick, M.S.; Jane M. Romm, M.S.; Alan F. Scott, Ph.D.; David Valle, M.D.; Chulan Kwon, Ph.D.; and Kimberly F. Doheny, Ph.D. Researchers from Jackson Laboratory in Bar Harbor, Me.; North York General Hospital in Toronto, Canada; The Hospital for Sick Children in Toronto, Canada; and KK Women's and Children's Hospital and Duke-NUS Graduate Medical School in Singapore also contributed to this work.

For more information:

http://www.hopkinsmedicine.org/heart_vascular_institute/research/training_grant/judge_lab/ http://www.hopkinsmedicine.org/profiles/results/directory/profile/0006961/daniel-judge

Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is a $6.7 billion integrated global health enterprise and one of the leading health care systems in the United States. JHM unites physicians and scientists of the Johns Hopkins University School of Medicine with the organizations, health professionals and facilities of The Johns Hopkins Hospital and Health System. JHM's vision, "Together, we will deliver the promise of medicine," is supported by its mission to improve the health of the community and the world by setting the standard of excellence in medical education, research and clinical care. Diverse and inclusive, JHM educates medical students, scientists, health care professionals and the public; conducts biomedical research; and provides patient-centered medicine to prevent, diagnose and treat human illness. JHM operates six academic and community hospitals, four suburban health care and surgery centers, and more than 30 primary health care outpatient sites. The Johns Hopkins Hospital, opened in 1889, was ranked number one in the nation for 21 years in a row by U.S. News & World Report.

Media Contacts: Stephanie Desmon; 410-955-8665; sdesmon1@jhmi.edu
Lauren Nelson; 410-955-8725; lnelso35@jhmi.edu

Stephanie Desmon | EurekAlert!

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>