Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular ‘Playbook’ for Halting Heart Failure Risk Factor Uncovered

24.09.2010
Scientists Showcase Steps to Stop Unwanted Enlargement of the Heart

Like a well-crafted football play designed to block the opposing team’s offensive drive to the end zone, the body constantly executes complex ‘plays’ or sequences of events to initiate, or block, different actions or functions.

Scientists at the University of Rochester Medical Center recently discovered a potential molecular playbook for blocking cardiac hypertrophy, the unwanted enlargement of the heart and a well-known precursor of heart failure.

Researchers uncovered a specific molecular chain of events that leads to the inhibition of this widespread risk factor.

The new research, published in Proceedings of the National Academy of Sciences, is a concept study in the very early stages of investigation and has yet to be examined in animal models. Nonetheless, it represents a new avenue of exploration for scientists working to find ways to prevent and treat cardiac hypertrophy and heart failure.

“While our findings are still in the beginning phases, they are important because heart failure is a major cause of human disease and death, and it remains very hard to treat,” said Zheng-Gen Jin, Ph.D., associate professor within the Aab Cardiovascular Research Institute at the Medical Center and lead author of the study. “One of the main treatments for heart failure, beta blockers, has huge side effects, such as increased fatigue and depression, so scientists need to continue to look for new ways to care for patients with the disease.”

The playbook begins with a key protein, histone deacetylase 5, or HDAC5, one of several proteins that influences gene expression – the process by which genes are turned on and converted into proteins that carry out the body’s functions. The location of HDAC5, in conjunction with other factors, helps determine whether or not gene expression takes place: If HDAC5 is pushed outside the nucleus, genes are turned on and proteins are made, but if it remains inside the nucleus genes are suppressed.

The major finding and linchpin in the playbook is the action of PKA, an enzyme that researchers found changes the composition of HDAC5, keeping it inside the nucleus of heart muscle cells and stopping the expression of cardiac fetal or cardiac growth genes – genes that spur the growth of a newly developing heart in a fetus, but also cause the growth of unwanted heart muscle cells in adults, making the organ bigger and thicker than it should be.

Researchers also believe PKA helps counteract stress signals, such as from high blood pressure, which interact with and typically boot HDAC5 out of the nucleus, clearing the way for the expression of cardiac growth genes and the subsequent development of heart muscle cells that lead to the enlargement of the heart.

Cardiac hypertrophy usually occurs when there is added stress on the heart. The most common cause of hypertrophy is hypertension, or high blood pressure, which forces the heart to work harder to pump blood throughout the body, causing the muscle to thicken over time. When the heart is enlarged, it does not work as efficiently as it should and can lead to heart failure.

According to Jin, next steps include animal studies to determine if keeping HDAC5 in the nucleus through PKA signaling stops cardiac hypertrophy in mice. Findings may reveal the HDAC5/PKA interaction as a viable target for drug therapy to treat cardiac hypertrophy and heart failure. Researchers have filed a patent application for the concept that is currently pending.

“Jin and his team have defined a new, potentially drugable target for treating cardiac hypertrophy, yet much more research is needed to determine if the findings hold beyond the current study,” said Joseph Miano, Ph.D., associate director of the Aab Cardiovascular Research Institute.

The study was funded by the National Institutes of Health. In addition to Jin, Chang Hoon Ha, Ph.D., Ji Young Kim, Ph.D., Jinjing Zhao, M.D., Ph.D., Weiye Wang, M.S., Bong Sook Jhun, Ph.D., and Chelsea Wong from the University of Rochester Medical Center contributed to the research.

For Media Inquiries:
Emily Boynton
585-273-1757
Email Emily Boynton

Emily Boynton | EurekAlert!
Further information:
http://www.urmc.rochester.edu
http://www.urmc.rochester.edu/news/story/index.cfm?id=2984

More articles from Health and Medicine:

nachricht 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

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

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>