Atrial fibrillation is a dysfunction arising in the aging heart that is associated with later cardiovascular disease; in this context it might be taken as an advance warning of the consequences of a growing burden of cell and tissue damage. As for many age-related conditions, there is a correlation with the chronic inflammation of aging. Lasting, unresolved inflammatory signaling changes the behavior of cells for the worse and is disruptive to tissue structure and function. Here, researchers identify the starting point of one specific pathway by which which inflammation disrupts the regulation of heart rhythm.
Chronic inflammation is a common denominator in many conditions associated with atrial fibrillation (AF). However, the exact mechanisms linking inflammation to arrhythmia have remained elusive. Interleukin-1 beta (IL-1β) - a molecule of the immune system involved in regulating inflammation - can directly influence the heart's electrical activity, creating a predisposition to AF. "The present work marks a key scientific milestone in the field of knowledge. Many review papers had already suggested that IL-1β could play a vital role in atrial fibrillation. We were able to demonstrate that this actually happens."
The research team began by analyzing the immunological profiles of 92 patients, including 30 healthy controls and 62 individuals diagnosed with AF. To delve deeper, the researchers used mice to investigate the effects of IL-1β. By administering controlled doses of IL-1β over 15 days, they simulated prolonged systemic inflammation. During observation, the rodents developed cardiac alterations that made them more susceptible to AF. Additionally, the team employed genetically modified mice lacking IL-1β receptors in macrophages - immune cells found throughout the body, including the heart. These animals did not develop AF, demonstrating that IL-1β triggers the condition by activating its receptors on macrophages.
The study also opens new avenues for treatment. Medications that inhibit IL-1β or caspase-1 - the enzyme that activates IL-1β production - are promising candidates to prevent AF in at-risk patients, particularly those with chronic inflammatory conditions.
Link: https://www.eurekalert.org/news-releases/1072499
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