An international team of scientists has identified a key protein that has the potential to reverse established cardiac fibrosis, the abnormal thickening of the heart valves, which progresses to heart failure.
Cardiac fibrosis occurs when healthy cardiac cells are replaced with fibrous connective tissue, causing scarring and a stiffer and less compliant cardiac muscle.
The researchers found that CCN5, a matricellular protein, can potentially be used for the development of new anti-cardiac fibrosis therapies.
"Our research is the first to demonstrate the ability to reverse cardiac fibrosis in heart failure models by targeting a specific gene," said lead researcher Roger Hajjar, professor at the Icahn School of Medicine at Mount Sinai in New York, US.
The findings, detailed online in the Journal of American College of Cardiology (JACC), demonstrated that CCN5 might provide a novel platform for the development of targeted anti-cardiac fibrosis therapies, which could benefit many patients with previously untreatable heart failure and other cardiovascular diseases.
"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," one of the researchers Woo Jin Park, professor at the Gwangju Institute of Science and Technology (GIST) in South Korea, said.
The team induced extensive cardiac fibrosis in experimental animal models of heart failure, and then proceeded to transfer CCN5 to the hearts.
Eight weeks later, they examined the cellular and molecular effects. The results revealed that CCN5 reversed cardiac fibrosis in the animals.
The therapeutic efficacy of CCN5 is now being investigated in pre-clinical models of heart failure with extensive fibrosis, the researchers said.
