In a Tufts-led study, researchers have explored the relationship between heart failure and immune cell activity, revealing unique T cell populations in mice with metabolic disorders that coincide with cardiac tissue abnormalities.
Using a mouse model that combines obesity and high blood pressure, the Tufts research team observed that these conditions yield the systemic activation of malfunctioning T cells—white blood cells that play a central role in the immune system.
That activation can stiffen the heart. But when investigators removed the overactive immune populations from the mice, cardiac function was partially restored. The work raises the possibility that detecting or modulating cardiac inflammation in vulnerable patients could slow the progression of heart disease.
“Our paper is starting to tease apart what T cells originating from the periphery of the body are actually doing in the heart,” said first author Sasha Smolgovsky, a Ph.D. candidate in immunology at the Graduate School of Biomedical Sciences at Tufts. Smolgovsky was awarded two fellowships to pursue this work, one from the National Institutes of Health and one from the American Heart Association.
“The heart is impacted almost as a secondary bystander,” Smolgovsky explained, “with the thickening of the tissue caused by inflammation leaving the heart unable to relax, thereby reducing cardiac output.”
This dysfunction, classified as heart failure with preserved ejection fraction (HFpEF), leaves the heart pumping blood but not relaxing enough to fill with a sufficient volume of blood. It is the slower-forming cousin of the better-known heart failure with reduced ejection fraction (HFrEF) typically seen in people who have just suffered a heart attack. HFpEF makes up about 50% of heart failure cases, but its pathology has been poorly understood. That’s something Smolgovsky and her colleagues are looking to address.
One of the study’s key findings is that the overactive T cells in the mouse model exhibited evidence of impaired resolution of cellular stress, which the research team want to explore as a potential clinical biomarker for HFpEF. They are also designing experiments to investigate how inflammation affects various types of heart cells to better characterize the role each plays in the disease.