New Mechanism of Cardiac Inflammation Discovered

Breakthrough in Cardiac Inflammation Research

Researchers at the University of California, San Diego, have uncovered a new mechanism of cardiac inflammation in a groundbreaking study that could transform heart attack treatment and help prevent the progression to heart failure. The research, led by Dr. Kevin King, an associate professor of bioengineering and medicine, focused on understanding inflammation in the borderzone of the infarcted heart—a region that has been largely understudied until now.

The Role of the Borderzone in Heart Inflammation

Traditionally, inflammation following a myocardial infarction (MI) has been attributed to professional immune cells like neutrophils and macrophages infiltrating the infarcted heart. However, the study's findings challenge this conventional understanding. The researchers discovered that the proinflammatory type I interferon (IFN) response was not initiated in the infarcted area where immune cells are concentrated, but rather in the borderzone surrounding the infarct.

This borderzone, where surviving heart muscle cells attempt to stabilize and proliferate after the injury, was found to be the primary site of inflammation. The team used advanced techniques such as single-cell RNA sequencing and spatial transcriptomics to isolate and study the cells in this challenging region of the heart.

Cardiomyocytes as Key Initiators of Inflammation

In a surprising twist, the study revealed that cardiomyocytes—heart muscle cells—were the dominant initiators of IFN signaling in the borderzone. The researchers found that these stressed cardiomyocytes often experienced nuclear envelope rupture, allowing nuclear DNA to escape and trigger an inflammatory response. This inflammation, in turn, weakened the heart wall, making it susceptible to dilation, thinning, and rupture. This finding offers a mechanistic explanation for the team's earlier observations that mice lacking IFN responses showed improved survival rates after MI.

Implications for Future Treatments

The findings suggest that targeting the IFN signaling pathway, limiting mechanical stress in the borderzone, and inhibiting DNA sensing could offer new therapeutic strategies to prevent heart failure in patients who have suffered a heart attack. Dr. King emphasized the importance of these new therapeutic targets, noting that many questions remain, but the potential to prevent heart failure post-MI is incredibly promising.

Conclusion

This research marks a significant advancement in our understanding of cardiac inflammation and opens up new avenues for treatment. By focusing on the previously overlooked borderzone of the infarcted heart, the team at UC San Diego has identified critical targets that could lead to better outcomes for heart attack patients, reducing the risk of heart failure and improving long-term survival.