A study lead by researchers from Johns Hopkins University of Medicine reveals a type of immune system T cell, eosinophil, appear to be partly responsible for heart muscle inflammation progressing to heart failure in mice.
The findings suggest for heart inflammation to occur, eosinophils do not need to be present, but they are required for the condition to progress to inflammatory dilated cardiomyopathy (DCMi) in mice. DCMi is a disease that causes the heart to become enlarged, so it cannot pump efficiently. The discovery will help researchers understand and learn more about the impact of eosinophils on heart function, says the researchers.
“Other studies have shown that people with high levels of eosinophils develop a number of heart diseases. This new work has provided more details about how these immune system cells may lead to deterioration of heart muscle function in mice in a way that lets us draw some parallels to human disease processes,” says Daniela Cihakova, M.D., Ph.D., associate professor of pathology at the Johns Hopkins University School of Medicine and the paper’s senior author.
Myocarditis, heart inflammation, often goes undiagnosed, because it is often asymptomatic, producing or showing no severe symptoms. A myocardial biopsy, a tiny sample of the heart muscle tissue is removed for testing, is required to determine the diagnosis. This makes it even more difficult to study the outcomes of the disease. Cihakova said, “We don’t understand why the hearts of some people will heal, while those of others develop chronic disease.”
The type of immune cell that dominates the inflammation of the heart determines the type of myocarditis. For example, innumerable eosinophils will infiltrate the heart in eosinophillic myocarditis. Whether or not some types of myocarditis are more likely to progress to DCMi than others is not known. However, the findings in this study shows when eosinophils are present in the heart in mice, the condition is more likely to lead to DCMi and if an abundance of eosinophils are present, the condition will lead to severe heart failure. The next step is to test if the same is true in humans, so physicians will be able to intervene early and prevent DCMi.
The research team first induced myocarditis in two different groups of mice, a group of mice that were genetically modified to be eosinophil-deficient and normal mice. The experimental autoimmune myocarditis method was utilized to induce the myocarditis. The process entails utilizing a peptide from heart muscle cells to initiate an immune response against the heart. The researchers discovered after 21 days, similar levels of acute inflammation in both groups of mice. Further testing revealed striking differences in the hearts of the two groups of mice, the eosinophil-deficient mice showed no signs of reduced heart function and the normal mice developed heart failure.
The leading author and Ph.D. student in the Bloomberg School of Public Health, Nicola Diny, said, “These surprising results told us that it is not the overall severity of inflammation, but rather the types of immune cells in the heart that decide whether myocarditis develops into heart failure.”
The hearts were also examined for fibrosis, which develops when heart muscles die in mammalians and humans. Fibrosis is scar tissue that is present in DCMi. Both groups of mice had similar degrees of scar tissue, even though the normal mice developed DCMi and the eosinophil-deficient mice showed no signs of reduced heart failure.
“This told us that in the absence of eosinophils, heart function can be preserved despite scar tissue formation,” Cihakova says. “It’s also important to note that although eosinophils accounted for just 1 to 3 percent of all heart-infiltrating cells in normal mice, this small percentage can still drive heart failure.”
The findings were published in The Journal of Experimental Medicine on March 16.