Groundbreaking Findings in Cardiovascular Inflammation Study
In a remarkable stride forward in cardiovascular research, the team at UC San Diego has identified a key factor contributing to inflammation in the heart, shedding light on new pathways for treating heart failure post myocardial infarction. Results from this study were showcased in the highly acclaimed publication Nature on August 28, 2024, pinpointing an unanticipated inflammatory response triggered by cardiomyocytes under stress. These cells border the necrotic region affected by a heart attack.
Ischemic heart diseases, characterized by insufficient blood supply to the cardiac muscle, stand as the principal cause of mortality globally. The inflammatory response induced by a heart attack can set the stage for heart failure. Anti-inflammatory medications have historically made little progress in combating heart failure, suggesting that the detailed mechanisms driving inflammation were yet to be discovered.
Revealing an Unknown Inflammatory Mechanism
Lead researcher Dr. Kevin King, a bioengineering and medicine associate professor at UC San Diego and a cardiologist with the Sulpizio Cardiovascular Center, has pinpointed the role of cardiomyocytes in sparking inflammation in the heart’s borderzone, which is near the damaged heart tissue. The underlying mechanism involves mechanical strain leading to the rupture of the nuclear envelope within the cardiomyocytes, consequently resulting in the leakage of nuclear DNA and the activation of type I interferon (IFN) pathways.
Dr. King notes the importance of the study’s findings, stating, “The significance of these revelations cannot be overstated. The borderzone is a critical area where our cardiac muscle cells are most at risk, and grasping how inflammation begins here could be central to devising treatments aimed at halting heart failure.”
Research was conducted using specialized mouse models with targeted gene deletions, complemented with cutting-edge genomic techniques like single-cell RNA sequencing and spatial transcriptomics. The research points to the possibility that blocking type I IFN pathways could mitigate the development of heart wall weakness, which is linked to hazardous conditions like dilatation, thinning, and tearing post-heart attack.
The investigation showcases potential new therapeutic methods focusing on mechanical distress, DNA detection, and IFN pathway signaling, with the ultimate objective to curb the detrimental effects of inflammation, which can aid in preventing heart failure in patients who have suffered a myocardial infarction.
The research received partial funding from the NIH DP2 New Innovator Award and presents a significant advancement in the battle against heart disease. The full study with its vital implications for heart disease treatment is available in the journal Nature, under the DOI: 10.1038/s41586-024-07806-1.
