Gene Targeting Reverses Heart Fibrosis In Mice

By using gene targeting to introduce the CCN5 protein into the heart, researchers have managed to reverse cardiac fibrosis in mice.

AsianScientist (Apr. 12, 2016) – Researchers in South Korea and the US have found that CCN5, a protein in the cell matrix, reverses established cardiac fibrosis in heart failure models. Their study was published in the Journal of American College of Cardiology.

Cardiac fibrosis occurs when fibrous connective tissue replaces healthy cardiac cells, causing scarring and stiffer and less compliant heart muscles. It is an independent predictor for the progression of heart failure, and while there currently are no effective cardiac fibrosis therapies available, it is considered a valid target for treatment.

The research team, led by Park Woo Jin, professor of life sciences at the Gwangju Institute of Science and Technology, South Korea and Roger J. Hajjar, professor of medicine at the Mount Sinai School of Medicine in the US, had previously established that CCN5 is significantly lower in the myocardium of patients with severe heart failure.

In the present study, they examined whether CCN5 can reverse cardiac fibrosis in experimental models as well. They induced extensive cardiac fibrosis in experimental animal models of heart failure and then proceeded to transfer CCN5 to the hearts. Eight weeks later, the team examined the cellular and molecular effects.

The results revealed that CCN5 reversed cardiac fibrosis in the models, with the researchers using trichrome staining and analyses of myofibroblast contents before and after CCN5 gene transfer to clearly show the reversal. Collectively, these data demonstrate that CCN5 could potentially be used for the development of new anti-cardiac fibrosis therapies.

“These findings demonstrate that CCN5 may provide a novel platform for the development of targeted anti-cardiac fibrosis therapies, which could benefit many patients with previously untreatable heart failure,” said Hajjar.

“Since CCN5 is a secreted protein, we may be able to deliver the CCN5 protein itself rather than the CCN5 gene in the form of recombinant virus or stem cells that are engineered to express CCN5,” said Park.

“The efficacy of these alternative approaches has yet to be tested, but they certainly deserve serious consideration.”



The article can be found at: Jeong et al. (2016) Matricellular Protein CCN5 Reverses Established Cardiac Fibrosis.

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Source: Mount Sinai School of Medicine; Photo: Shutterstock.
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