Researchers at Vanderbilt University recently studied the inflammation phase after heart attacks and identified a protein, cadherin-11, that is significantly involved in the inflammation in cardiac fibrosis.
When people survive heart attacks, technically called myocardial infarction, the healing phase is complicated, involving remodeling and repair, called the granulation phase. But the body simultaneously responds with inflammation and scarring, which also decreases cardiac function and increases the risk of future heart attacks, including heart failure.
Researchers at Vanderbilt University recently studied the inflammation phase after heart attacks and identified a protein, cadherin-11, that is significantly involved in the inflammation in cardiac fibrosis. Previous work by the researchers show a specific antibody could target cadherin-11 to prevent calcific aortic valve disease (CAVD). CAVD is a slow, pressive disorder that varies from mild valve thickening of the heart without blocking blood flow to severe calcification that causes aortic stenosis.
The research was published in the journal JCI Insight.
“Some amount of inflammation is necessary in myocardial infarction, but becomes excessive and causes adverse side effects,” said senior author W. David Merryman, Walters Family Chair in the School of Engineering and a Professor of Biomedical Engineering, Pharmacology, Medicine, and Pediatrics, at Vanderbilt. “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.”
The researchers worked in a mouse model, inducing myocardial infarction in mice who were either heterozygous or homozygous knockout of CDH11, so-called “normal” mice receiving bone marrow transplants from animals that did not have Cdh12, or normal mice treated with an antibody against CDH11 (SYN0012).
SYN0012 blocks the cadherin-11 protein and in the Vanderbilt studies, was supplied by the Roche Innovation Center in Basel, Switzerland. Roche had been investigating SYN0012 in rheumatoid arthritis but pulled it from its pipeline last year.
Shortly after a heart attack, immune cells are stimulated to stabilize the heart and clear cellular debris. Once done, signaling results in inflammation and cells called myofibroblasts start remodeling cardiac tissue. By using SYN0012, they could fine-tune the amount of inflammation involved in the remodeling, which allowed the heart more freedom to recover and return to normal.
“Our studies using this antibody noted improvements in every metric,” said Merryman. “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.”
Similar research reported this week out of the University of California – San Diego, showed that use of an injectable hydrogel was able to repair damage and restore heart function in patients after a heart attack. This was a Phase I clinical trial sponsored by Ventrix, a UCSD spin-off.
The gel, named VentriGel, is manufactured from cardiac connective tissue from pigs. The researchers take the tissue, strip out heart muscle cells, then freeze-dry and grind it into powder, then liquify into a fluid that allows it to be injected into the heart muscle without surgery. At room temperate the liquid become a semi-solid, porous gel.
The Phase I trial was in 15 people who had moderate damage in the left ventricle chamber of the heart after a heart attack.
“Although the study was designed to evaluate safety and feasibility and not designed to show whether VentriGel effectively helps improve heart function, we observed some improvements in patients,” said Karen Christman, the study’s senior author and a professor of bioengineering at UCSD. “For example, patients could walk longer distances. We also observed signs of improving heart function in patients who experienced a heart attack more than one year prior to treatment.”
VentriGel was invented by Christman and her research group. She co-founded Ventrix with the company’s chief executive officer Adam Kinsey, which licensed the technology from UCSD.
