Antibody could fine-tune recovery from heart attack


An antibody initially developed for rheumatoid arthritis may offer a way to fine-tune recovery after a heart attack and decrease the risk for heart failure, research with mice shows.

More than one million Americans per year experience myocardial infarction, commonly known as a heart attack, and the healing and rebuilding phase that begins shortly thereafter—a complicated process which involves remodeling and repairing the heart.

This process is known as the granulation phase and is critical for healing. But due to inflammation and scarring, this phase simultaneously reduces cardiac function, significantly increasing the risk of future cardiac events, including heart failure.

The study, published in JCI Insight, looks at the inflammation phase after myocardial infarction events and is the first to target a specific protein, known as cadherin-11— a major contributor to inflammation in cardiac fibrosis.

Researchers say the new findings are significant as they build on existing work looking at cadherin-11, including a 2017 paper which showed how this particular antibody targets cadherin-11 to prevent calcific aortic valve disease.

“Some amount of inflammation is necessary in myocardial infarction, but becomes excessive and causes adverse side effects,” says senior author W. David Merryman, professor of biomedical engineering, pharmacology, medicine, and pediatrics at Vanderbilt University.

“This latest work with the antibody shows a new ability to maintain more precise control over the amount of inflammation in the fibrotic remodeling process, which yields reduced scarring and improved cardiac function.”

Here’s how it works: In the aftermath of myocardial infarction, immune cells are first recruited to assist in stabilizing and clearing the heart of debris. Once that process is complete, signaling begins for inflammation to kick in and cells known as myofibroblasts begin remodeling.

When they used the antibody developed to block cadherin-11 in patients with rheumatoid arthritis, the researchers could similarly target and fine-tune the level of inflammation in cardiac recovery—which allowed the heart to better recover and return to operating at a healthier pace.

Researchers have already tested the antibody for clinical use, Merryman says, and thanks to the new research, will likely generate excitement as a post-myocardial infarction treatment.

“Our studies using this antibody noted improvements in every metric,” Merryman says. “Starting with calcific aortic valve disease and now with myocardial infarction, we’ve seen significant improvements from short-term heart function to long-term prevention of progression into heart failure. This antibody is a major step forward for cardiac recovery.”

The National Institutes of Health, the National Science Foundation, the American Heart Association, and the Leducq Foundation funded the work.

Source: Vanderbilt University



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