The scientists will investigate if and how the proteins in the heart change in the event of heart failure. (Photo: <a href="http://www.shutterstock.com/pic-232532455/stock-photo-businessman-having-heart-attack.html" target="_blank">Shutterstock</a>)
The scientists will investigate if and how the proteins in the heart change in the event of heart failure. (Photo: Shutterstock)

New research project sets its sights on cure for heart failure

Modern medicine can only slow down development of heart failure, but not prevent it. New project aims to change that.

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Around 20 million people suffer from heart failure every year and many of them die. Doctors have no means to prevent it from happening -- they can only postpone the inevitable.

Scientists behind a new research project want to change this and have set out to create the basis for better treatment of the condition.

They hope to accomplish this by looking at how proteins inside the heart’s cells undergo change in the event of heart failure, says project leader Alicia Lundby, a postdoc at the Centre for Protein Research, University of Copenhagen. Previous research has shown that some of these specific proteins are not working as they should in patients with heart failure and herein lies the key to cracking the case.

"The reason why we still don’t have a medical cure for heart failure is that we still don't fully understand what’s going on at the molecular level in the heart in the event of heart failure,” says Lundby. “My guess is that there are far more proteins involved in in the condition than the ones we are already familiar with.”

Mice heart failure clue to condition in humans

The first step is to investigate if and how the proteins change in the event of heart failure. For obvious reasons, this cannot be studied in humans, which is why the first experiments are being conducted on mice.

"If you tighten a thin cord around the aorta of a mouse it will develop heart failure eight weeks later,” says Lundby. “We will be investigating how the proteins in the heart of these mice differ from those in mice which have undergone the same intervention, but where the cord wasn’t tightened.”

Simultaneously, Lundby will examine how the proteins inside the mice’s hearts are affected when they’re treated with the same type of medicine as is given to human patients with heart failure.

They will study both the acute effects of the medicine and its effects on the heart’s proteins in the long term.

Although scientists already know that changes occur when we administer heart medicine, says Lundby, we don’t know which proteins respond positively to the medication.

"It's my hope that by mapping the changes in the proteins we can ultimately target heart medicine more efficiently, so that it has a broad effect on the heart while having a specific impact on the most important proteins,” she says.

Could be the first step towards a cure

The study is primarily about building the foundations for future research and the development of new medicines.

Although the advanced technology facilitates the study of thousands of proteins at once, the scientists are still likely to be left with a lot of work to do before their results can be used by the pharmaceuticals industry.

"If we're very lucky we'll be left with very few deviant proteins in the sick hearts and we’ll be able to investigate whether medicines targeted at precisely one of these proteins can change the condition [of heart failure],” says Lundby. ”My guess, though, is that we'll find somewhere in the region of 100 proteins which change in some way or another, which means we'll still have to find out which of the proteins determines whether the condition will occur."

Lundby does, however, have a possible solution to this.

Along with colleagues from the Broad Institute in the US, which is affiliated with Harvard and MIT, she has developed a special technique that can further narrow the field of potentially important proteins.

"We've developed a statistical analysis tool that makes it possible to link the results from this type of proteomics experiment, based on animal tissue, with data from the genetic studies of humans,” says Lundby.

By correlating the results from the two different types of dataset she will be able to make a qualified guess as to which genes are most likely central to her study.

“Next, we can isolate the gene in, let's say, zebra fish and directly examine the effect of the gene on cardiac function and thus either confirm or reject our assumption,” she says.

Technique can be used on other organs

No matter what the outcome of the project, the results will enhance our understanding of what regulates the heart at the molecular level. And that knowledge will help increase the chance of developing better heart medicine.

At the same time, the actual method of extracting proteins from tissue samples from animals or from human biopsies probably also help scientists not involved in heart research.

"The proteomics methods we have developed are still very new and are therefore not yet particularly widely used,” says Lundby. “I have been focusing on heart tissue because that’s my primary field but the technique can easily be applied to other types of tissue.”

"This type of experiment takes a long time but I would be very surprised not to see our approach used in other studies of proteins associated with diseases in other organs," says Lundby.

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Read the original story in Danish on Videnskab.dk

Translated by: Hugh Matthews

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