The progression of coronary artery disease atherosclerosis (CAD) is closely associated with cardiomyocyte apoptosis and inflammatory responses. This study focused on investigating the impact of BRCA1 in exosomes (Exo) derived from M1 macrophages on CAD. Through the analysis of single-cell RNA-seq datasets, significant communication between macrophages and cardiomyocytes in CAD patients was observed. BRCA1, identified as a significant apoptosis-related gene, was pinpointed through the assessment of differential gene expression and weighted gene co-expression network analysis (WGCNA). Experimental procedures involved BRCA1 lentivirus transfection of M1 macrophages, isolation of Exo for application to cardiomyocytes and smooth muscle cells, cell viability assessments, and characterization of Exo. The results showed that BRCA1-Exo from M1 macrophages induced cardiomyocyte apoptosis and affected smooth muscle cell behavior. In vivo studies further supported the exacerbating effects of BRCA1-Exo on CAD progression. Overall, the involvement of Exo carrying BRCA1 from M1 macrophages is evident in the induction of cardiomyocyte apoptosis and the regulation of smooth muscle cell behaviors, thereby contributing to CAD atherosclerosis progression. These findings unveil novel molecular targets that could have potential implications for CAD treatment strategies.