Research uncovers new steps on pathway to enlarged heart

October 23, 2008

Researchers have new insight into the mechanisms that underlie a pathological increase in the size of the heart. The research, published by Cell Press in the October 24th issue of the journal Molecular Cell, may lead to the development of new strategies for managing this extremely common cardiac ailment that often leads to heart failure.

High blood pressure, heart valve disease and heart attacks can lead to a abnormal thickening of the heart muscle, called myocardial hypertrophy. At the molecular level, signals driving myocardial hypertrophy, such as elevated levels of catecholamine hormones (i.e. adrenaline), activate the Myocyte Enhancer Factor (MEF) proteins. This alters gene expression in heart muscle cells and induces an adverse developmental paradigm known to cardiologists as the "fetal gene response".

"Previous research has shown that the signaling pathways leading to MEF2 are altered during pathological cardiac hypertrophy," says senior study author Dr. John D. Scott, a Howard Hughes Medical Institute Investigator from the Department of Pharmacology at the University of Washington. "Although we know that enzymes called histone deacetylases (HDACs) control MEF2 activity, it was not clear that HDACs and MEF2 were integrated into a larger signaling unit."

To further identify the molecular mechanisms associated with cardiac hypertrophy, Dr. Scott and colleagues studied cardiac A-Kinase Anchoring Proteins (AKAPs), which are known to play a critical role in organizing signaling complexes in response to catecholamine hormones and transmitted signals within cells.

The researchers found that AKAP-Lbc functions as a scaffolding protein that selectively directs catecholamine signals to the transcriptional machinery to potentiate the hypertrophic response. "Our study supports a model where AKAP-Lbc facilitates activation of protein kinase D, which in turn phosphorylates the histone deacetylase HDAC5 to promote its export from the nucleus. The reduction in nuclear HDAC5 favored MEF2 transcription and the onset of cardiac hypertrophy."

These studies reveal a role for AKAP-Lbc in which increased expression of the anchoring protein selectively amplifies a signaling pathway that drives cardiac muscle cells to a pathophysiological outcome. "It will be important to explore the role of the AKAP-Lbc/PKD/HDAC5 signaling pathway in whole animal models to establish whether AKAP-Lbc is a valid biomarker for hypertrophic cardiomyopathy and to determine which genes are initiated upon up-regulation of the anchoring protein," offers Dr. Scott.
-end-


Cell Press

Related Heart Muscle Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Muscle protein abundant in the heart plays key role in blood clotting during heart attack
A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows.

Heart muscle cells change their energy source during heart regeneration
Researchers from the Hubrecht Institute (KNAW) have found that the muscle cells in the heart of zebrafish change their metabolism during heart regeneration.

New study may have the reason why heart medication gives muscle pain
The McMaster research team found muscle cells treated with statins released the amino acid called glutamate at much higher levels than muscle cells that were untreated.

Vitamin E found to prevent muscle damage after heart attack
Early studies from scientists at the Baker Heart and Diabetes Institute in Australia and Jena University in Germany have found Vitamin E could be used to save the muscle from dying during a heart attack.

A simple method to improve heart-attack repair using stem cell-derived heart muscle cells
The heart cannot regenerate muscle after a heart attack, and this can lead to lethal heart failure.

What is known -- and not known -- about heart muscle diseases in children
Cardiomyopathies (heart muscle diseases) in children are the focus of a new scientific statement from the American Heart Association that provides insight into the diagnosis and treatment of the diseases as well as identifying future research priorities.

Being overweight as a teen may be associated with higher risk of heart muscle disease in adulthood
The risk of developing cardiomyopathy, which often leads to heart failure, increased in adult Swedish men who were even mildly overweight around age 18.

Heart patch could limit muscle damage in heart attack aftermath
Guided by computer simulations, an international team of researchers has developed an adhesive patch that can provide support for damaged heart tissue, potentially reducing the stretching of heart muscle that's common after a heart attack.

UA scientist identifies cellular gene signatures for heart muscle regeneration
A research team led by Jared Churko, PhD, director of the University of Arizona iPSC Core in the UA Sarver Heart Center, used a transcriptomic approach -- studying what genes are expressed -- to identify gene signatures of cell subpopulations identified as atrial-like or ventricular-like.

Read More: Heart Muscle News and Heart Muscle Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.