<i>In vivo</i>, Ang II induced autonomic remodeling, Ca2+-handling suppression, increased apoptosis with CD47/SIRPα upregulation, impaired efferocytosis, and heightened inflammatory signaling; valsartan partially reversed these changes.<h4>Discussion</h4>Multi-omics and <i>in vivo</i> evidence suggests an ANS-immune-atrial remodeling axis in which CD47-SIRPα-dependent efferocytosis blockade is highly associated with atrial inflammation and AF susceptibility, with valsartan acting as a clinically relevant modulator of this pathway. Here, SIRPA is linked to atrial fibrillation.