Acute Myocardial Infarction and Ischemic Stroke as Systemic Accelerators of Atherosclerotic Plaque Inflammation and Vulnerability.

Abstract

Acute ischemic cardio-cerebrovascular events are critical clinical emergencies characterized by sudden interruption of arterial blood supply to the myocardium or cerebral tissue, predominantly presenting as acute myocardial infarction and ischemic stroke. Individuals affected by these events exhibit a significantly elevated risk of recurrence, particularly during the critical timeframe spanning the initial weeks to months following the primary incident. Accumulating evidence reveals that, in the aftermath of acute ischemic events, endothelial senescence and sustained endothelial dysfunction are mediated by trained immunity, alongside signaling cascades activated by exosome-derived ligands and neutrophil extracellular trap (NET)-derived cell-free DNA-most notably encompassing the Notch1 pathway and the high mobility group box 1-receptor for advanced glycation end products (HMGB1-RAGE) axis. Furthermore, neuroendocrine responses coupled with glucose metabolic dysregulation contribute to systemic inflammation and promote atherosclerotic progression. Current preclinical models highlight the therapeutic efficacy of multifaceted interventions, ranging from targeted interventions and immunomodulation to chemokine-receptor blockade. Consequently, this review elucidates the underlying mechanisms promoting post-ischemic plaque destabilization and systematically evaluates therapeutic strategies designed to minimize recurrence and optimize long-term patient outcomes.