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 Antibiotic effective against drug-resistant bacteria in pediatric skin infections
17.02.2017 | University of California - San Diego

nachricht Tiny magnetic implant offers new drug delivery method
14.02.2017 | University of British Columbia

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>