Protein injections could finally repair muscle after a heart attack

This is the first time researchers have developed a means to reverse the loss of elasticity in damaged heart tissue.
Deena Theresa
Human heart stock photo.
Human heart stock photo.

volkan arslan/iStock 

Cardiovascular diseases are the largest cause of death globally. 

The aftermath of a heart attack results in damaged heart muscle, which, over time, becomes a scar. This scar tissue can cause complications with pumping and transporting blood as it does not have the elasticity and flexibility of a healthy heart muscle and cannot revert to the original.

Until now.

For the first time, an international of researchers at the University of Sydney has developed a method — a protein injection — to reverse the loss of elasticity of damaged heart tissue following heart attacks.

The protein building block in question, tropoelastin, can 'turn back the clock' on muscle damage, making the scars' stretchier' and helping improve the heart's ability to contract, according to the release.

This is also the first time scientists have investigated the potential of tropoelastin in treating heart disease.

Protein injections could finally repair muscle after a heart attack
The paper’s visual abstract.

Investigating the potential of the protein

"This research showcases the potential of tropoelastin in heart repair and suggests further work will show exciting possibilities of its role in future treatments and therapies," lead researcher Dr. Robert Hume who conducted the research at the Westmead Institute for Medical Research, said in a statement.

In preclinical studies, the researchers injected purified tropoelastin in the wall of the heart in rats days after a heart attack was induced. 

A new surgical method utilizing ultrasound guided the needle into the heart wall, which is known to be less invasive than previous methods. 

Twenty-eight days later, the heart muscle that was originally damaged and scarred at the beginning regained its elasticity and resembled muscle function similar to before the heart attack.

"Tropoelastin can repair the heart because it is a precise replica of the body's natural elastic protein," said co-author Professor Anthony Weiss from the Charles Perkins Center and Faculty of Science.

Tropoelastin was found to reduce scar size and revert the muscle to its original form

Upon conducting further tests, the researchers found that tropoelastin reduced scar size and stabilized it by increasing its elastin content and therefore decreasing the stiffness of the scar.

The researchers also conducted further experiments on human cardiac fibroblasts in a petri dish. After being treated with tropoelastin, the cells were found to generate elastin, which gives human tissue elasticity and the capacity to stretch.

"What we have found is highly encouraging. We hope to continue developing the method so it can eventually be used in a clinical setting and used to treat and improve the lives of the millions of heart failure patients worldwide," said senior author Associate Professor James Chong.

The results of the study are published in Circulation Research.

Study Abstract:

Background: Myocardial infarction (MI) is among the leading causes of death worldwide. Following MI, necrotic cardiomyocytes are replaced by a stiff collagen-rich scar. Compared to collagen, the extracellular matrix protein elastin has high elasticity and may have more favorable properties within the cardiac scar. We sought to improve post-MI healing by introducing tropoelastin, the soluble subunit of elastin, to alter scar mechanics early after MI.

Methods and Results: We developed an ultrasound-guided direct intramyocardial injection method to administer tropoelastin directly into the left ventricular anterior wall of rats subjected to induced MI. Experimental groups included shams and infarcted rats injected with either PBS vehicle control or tropoelastin. Compared to vehicle treated controls, echocardiography assessments showed tropoelastin significantly improved left ventricular ejection fraction (64.7±4.4% versus 46.0±3.1% control) and reduced left ventricular dyssynchrony (11.4±3.5 ms versus 31.1±5.8 ms control) 28 days post-MI. Additionally, tropoelastin reduced post-MI scar size (8.9±1.5% versus 20.9±2.7% control) and increased scar elastin (22±5.8% versus 6.2±1.5% control) as determined by histological assessments. RNA sequencing (RNAseq) analyses of rat infarcts showed that tropoelastin injection increased genes associated with elastic fiber formation 7 days post-MI and reduced genes associated with immune response 11 days post-MI. To show translational relevance, we performed immunohistochemical analyses on human ischemic heart disease cardiac samples and showed an increase in tropoelastin within fibrotic areas. Using RNA-seq we also demonstrated the tropoelastin gene ELN is upregulated in human ischemic heart disease and during human cardiac fibroblast-myofibroblast differentiation. Furthermore, we showed by immunocytochemistry that human cardiac fibroblast synthesize increased elastin in direct response to tropoelastin treatment.

Conclusions: We demonstrate for the first time that purified human tropoelastin can significantly repair the infarcted heart in a rodent model of MI and that human cardiac fibroblast synthesize elastin. Since human cardiac fibroblasts are primarily responsible for post-MI scar synthesis, our findings suggest exciting future clinical translation options designed to therapeutically manipulate this synthesis.

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