Researchers here note a mechanism that causes T cells of the adaptive immune system to spur chronic inflammation and tissue damage following a heart attack. As the researchers note, not all inflammation is the same. Some is maladaptive, and this is particularly the case in older individuals. The aged immune system is more prone to a sustained inflammatory response, provoked by pro-inflammatory signaling of senescent cells and the signs of cell damage that circulate in the body. Suppressing all inflammation is too blunt of a tool, however, as short-term inflammation is still necessary for regeneration and response to pathogens even in later life.
Inflammation is supposed to help protect us - it's part of an immune response to fight off pathogens and clear infections. But patients with cardiac disease often have chronic inflammation that damages their hearts, even with no infection present. When a heart attack or other issue damages the heart and leaves it unable to pump enough blood to meet the body's needs, the heart tries to compensate by pumping faster. The cardiac muscle cells have to work harder and this stress causes them to release molecules known as reactive oxygen species. Looking at the hearts of mice, the researchers determined that products of these reactive oxygen species modify proteins in the heart so that the immune system views them as a potential threat.
"The formation of these new targets is what we found that our T cells are robustly responding to. And this ultimately leads to inflammation that affects the heart." The researchers confirmed that these modified proteins also appeared in the cardiac tissue of human patients whose hearts were failing. Chronic inflammation can cause structural changes to the heart - the muscle can become enlarged or develop fibrous tissue, impeding its ability to pump blood efficiently and leading to further deterioration. But anti-inflammatory treatments or attempts to broadly target reactive oxygen species have yet to be successful. They often end up interfering with other aspects of the immune system or necessary physiological processes.
With this improved understanding of how T cells are being activated in patients with heart disease, the researchers hope to develop more targeted treatments. They have already tested one possibility in mice: an agent that binds to the specific molecules altering cardiac proteins.