Despite major advances in acute reperfusion therapies, patients surviving ischemic stroke or myocardial infarction remain at high risk for long-term cardiovascular and metabolic comorbidities. Emerging evidence identifies trained immunity, the long-lasting reprogramming of innate immune progenitors, as a central driver of this interorgan communication. Sterile insults such as stroke or myocardial infarction imprint persistent inflammatory memory via long-lasting reprogramming of bone marrow hematopoietic progenitors, biasing myelopoiesis and generating proinflammatory monocytes that target distant organs. This central trained immunity explains how a single ischemic event can precipitate cardiac dysfunction, accelerate atherosclerosis, or exacerbate metabolic disease, thereby contributing to multimorbidity in vascular patients. Understanding these systemic immune circuits provides a conceptual framework for developing interventions that interrupt maladaptive inflammatory memory. Finally, we discuss emerging therapeutic strategies to prevent maladaptive innate immune memory and mitigate chronic vascular inflammation and multimorbidity.
Arthur Liesz (Thu,) studied this question.