Strokes have long been associated with acute brain injury, but their effects extend far beyond the initial event, influencing long-term health across multiple organs, especially the heart. Emerging research suggests that systemic inflammation following a stroke plays a crucial role in developing chronic comorbidities, such as cardiac dysfunction.
A study published in Cell has shed light on a surprising connection between brain injury from a stroke and heart health. Researchers have discovered that specific immune cells, known as myeloid cells, can retain a “memory” of the brain injury, leading to long-term inflammation in the heart. This inflammation is driven by changes in gene expression patterns within these cells, which are regulated by epigenetic mechanisms.
Epigenetics refers to heritable changes in gene expression that do not alter the DNA sequence. These changes are driven by mechanisms such as DNA methylation, histone modifications, and non-coding RNA interactions, which regulate gene activity. Influenced by environmental and lifestyle factors, epigenetic changes are crucial in development, cell differentiation, and disease. Unlike DNA mutations, epigenetic modifications are reversible, making them potential targets for therapies in conditions like cancer, neurological disorders, and cardiovascular disease.
Previous articles have reviewed the relationship between DNA methylation and heart failure, as well as DNA methylation’s involvement with brain immune cells. The current study, led by Professor Arthur Liesz from the Institute for Stroke and Dementia Research (ISD) at LMU University Hospital, focused on understanding how brain injury can lead to cardiac dysfunction and the epigenetic modifications associated with it.
The medical burden of stroke isn’t limited to the brain; patients often face a cascade of health issues in the months and years following the event. According to the study, more than 60% of stroke survivors experience heart-related complications, such as arrhythmias and cardiac dysfunction. Liesz and his team hypothesized that the high incidence of comorbidities following a stroke might share a common immunological origin. Their findings confirmed their theory that dysfunctions in other parts of the body originate from the immunological memory of blood-forming cells in the bone marrow.
Using advanced techniques, like single-cell sequencing, the researchers observed persistent pro-inflammatory changes in monocytes and macrophages across several organs, including the heart. These immune cells, typically responsible for responding to infections, were found to be epigenetically reprogrammed by the stroke, leading to a state of chronic inflammation that persisted for months after the initial brain injury.
The study identified IL-1β, a key pro-inflammatory cytokine, as the main driver of these epigenetic changes. These IL-1β-induced modifications in immune cells were not only observed in stroke patients but were also transferrable to healthy mice, causing them to develop cardiac fibrosis (scarring) and diastolic dysfunction (impaired pumping function)—conditions typically seen in heart disease. When the researchers blocked IL-1β in mice, it prevented both cardiac fibrosis and systemic inflammation, successfully preventing cardiac problems after stroke.
“These findings are hugely significant,” emphasized Liesz, “as they open up the promise of effective therapeutic approaches for the prevention of secondary cardiac conditions after a stroke.”
The researchers believe that the epigenetic changes observed after a stroke reprogram the immune system, offering a new explanation for how IL-1β contributes to various health issues. By linking the brain and heart, their findings reveal that stroke-related immune changes can have widespread effects. This understanding may clarify the causes of IL-1β-related conditions, such as heart problems and chronic inflammation, while also suggesting new treatment options and enhancing our approach to preventing long-term complications from brain injuries.
Source: Alba Simats, et al. Innate immune memory after brain injury drives inflammatory cardiac dysfunction. Cell. August 22, 2024.
Resource: Ludwig-Maximilians-Universität München. Brain-heart axis: Strokes change epigenetics of immune system. 23 July 2024.
