In the aftermath of a heart attack, the body's own defenses may contribute to future heart failure. "The body tries to fix the injury to the heart muscle by depositing the fibers, but this causes a greater problem," says Dr. Thomas Sato, co-senior author of the study. "This process, called fibrosis, causes the heart to become like steel, unable to contract and pump blood throughout the body. The result can be fatal."
Sato and his team removed from a mouse's genome a gene called Sfrp2, stopping the mice from producing the protein sFRP2. They found that there was less scar tissue formed in the hearts of mice without the gene, compared to normal mice that still had the gene within their DNA.
The experimental mice also had improved recovery to their heart function, which leads the authors to believe that the protein has a direct affect on muscle scarring and stiffening following myocardial infarction.
The researchers then determined how the main component of connective tissue, collagen, interacts with the sFRP2 protein, and how these molecules play a crucial role in scar formation. "With many injuries and diseases, large amounts of collagen are formed and deposited in tissues, leading to scarring and fibrosis," says Dr. Greenspan, an expert in collagen.
Together, the researchers found that the sFRP2 protein works by accelerating the processing of pro-collagen, a precursor of mature collagen, the main component deposited in scar tissue. Following a heart attack, fibrous collagen deposits are increased, replacing the dead muscle and leading to more scar tissue, which prevents recovery.
"Therapeutically, the findings mean that it is possible to create a drug that may one day inhibit the functioning of the protein in order to limit fibrosis within the heart," says Sato. "Doing so may aid in controlling the degree of scarring."