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Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Atrial fibrillation (AF) is the most common and clinically significant arrhythmia requiring treatment. Although an imbalance between the sympathetic and vagal branches of autonomic nervous system (ANS) is known to trigger and sustain AF, the underlying mechanisms remain incompletely understood. Furthermore, there are yet no clinically authorized antiarrhythmic drugs currently targeting the modulation of ANS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Targeted LC\u2013MS\/MS profiling of plasma 39 neurotransmitters was conducted in a clinical cohort. To identify shared mechanisms, atrial transcriptomes and a sympathetic neuron activation dataset were integrated with DEGs, WGCNA, enrichment, immune infiltration, and machine-learning feature selection, and in silico docking was performed. For\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation, an Ang II\u2013infused mouse model with valsartan intervention was utilized, including transesophageal burst pacing, immunostaining, immunoblotting, and efferocytosis quantification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Plasma from AF patients exhibited an autonomic-imbalance signature (upregulated monoaminergic and downregulated cholinergic neurotransmitters). Shared ANS\u2013AF bioinformatic analysis highlighted hub genes as CDKN2D, FYTTD1, LRR1, and POPDC3. Immune analyses pinpointed CD47-mediated efferocytosis as a crucial link.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , Ang II induced autonomic remodeling, Ca\u00b2\u207a-handling suppression, increased apoptosis with CD47\/SIRP\u03b1 upregulation, impaired efferocytosis, and heightened inflammatory signaling; valsartan partially reversed these changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Multi-omics and\n                      <jats:italic>in vivo<\/jats:italic>\n                      evidence suggests an ANS\u2013immune\u2013atrial remodeling axis in which CD47\u2013SIRP\u03b1\u2013dependent efferocytosis blockade is highly associated with atrial inflammation and AF susceptibility, with valsartan acting as a clinically relevant modulator of this pathway.\n                    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