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Study reveals 'signature of heart failure'

November 13, 2006 By Erika Check This article courtesy of Nature News.

Tell-tale pattern of RNA expression could lead hunt for better treatments.

The pain of a love affair gone bad can cause a broken heart. And so can a type of molecule called a micro RNA, researchers report today.

MicroRNAs (miRNAs) are small organic chemicals found in the body. They are encoded by DNA, and after they are read out from the genome, the miRNAs are chopped into short pieces that increase or dampen down the production of specific proteins. Scientists know that this type of regulation plays an important role in development and in the growth of certain cancers.

Today, researchers open a new vista for miRNA research by reporting that the small chemicals are also important in heart disease, the number-one cause of death and disability of adults in developed countries.

A team led by Eric Olson at the University of Texas Southwestern Medical Center in Dallas used an miRNA microarray - a plate loaded with samples of 186 different miRNA molecules. His team used the microarray to examine heart tissue from two different mouse models of cardiac hypertrophy a condition in which heart cells become larger than normal, which often leads to heart disease and heart failure. The team found a signature of 11 miRNAs that were more abundant than normal in both mouse models.

It's opened up a new direction for us to think about how heart disease occurs.
Eric Olson, University of Texas Southwestern Medical Center
When the researchers examined tissue from failing human hearts, they found that five of these same miRNAs were also particularly abundant. And when they over-expressed these miRNAs in cells in a culture dish, or in mouse models, they found it could force heart cells to become enlarged, resulting in heart failure1.

Up-beat scientists

That suggests to Olson that his team may have identified the microRNA signature of heart failure. "We learned that there is an entirely unknown mechanism of regulation by which the heart controls its growth and its function, and that's through utilizing these microRNAs," Olson said. "That's opened up a new direction for us to think about how heart disease occurs."

The researchers don't yet know which proteins the miRNAs are controlling, but they are trying to find out. That could lead to the development of better treatments for heart disease.

Scientists say this study is the leading edge of a wave of research that is expected to find roles for miRNAs in many other diseases. The miRNA microarrays have been available commercially for only a year, and as miRNAs are known to be extremely important to development and some cellular processes, such as cell death, scientists are trying to figure out exactly which are involved in disease.

We can expect to see a growing number of studies like this, predicts Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco.

"It's a good example of how microRNAs are likely to be important to various physiological insults that play a role in disease processes," Srivastava says.

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  1. Van Rooij E., Sutherland L. B., Liu N.& Williams A. H., et al. Proc. Natl. Acad. Sci. USA, Published online 13 November (doi: 10.1073)(2006).


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