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 Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

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: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>