Exosome-mediated effects of BRCA1 on cardiovascular artery disease

被引：0
作者：
Yu, Hairui [1 ]
Wei, Dong [1 ]
Liao, Weiqian [2 ]
Shang, Xiaoming [2 ]
Li, Dandan [2 ]
Liu, Chunzhao [1 ]
Deng, Qimei [1 ]
Huangfu, Haiquan [2 ]
机构：
[1] Shanghai Univ Tradit Chinese Med, Dept Prevent Med, Shenzhen Hosp, Shenzhen 518000, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Dept Cardiol, Shenzhen Hosp, Shenzhen 518000, Peoples R China
来源：
CELL BIOLOGY AND TOXICOLOGY | 2025年 / 41卷 / 01期
关键词：
Coronary artery disease; Atherosclerosis; BRCA1; Exosomes; Cardiomyocyte apoptosis; Smooth muscle proliferation; SMOOTH-MUSCLE-CELLS; CANCER;
D O I：
10.1007/s10565-025-09996-4
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
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页数：31
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  • [1] Alsiary R., Brownhill S.C., Bruning-Richardson A., Hutson R., Griffin N., Morrison E.E., Et al., Expression analysis of the MCPH1/BRIT1 and BRCA1 tumor suppressor genes and telomerase splice variants in epithelial ovarian cancer, Gene, pp. 34-44, (2018)
  • [2] Arya S.B., Chen S., Jordan-Javed F., Parent C.A., Ceramide-rich microdomains facilitate nuclear envelope budding for non-conventional exosome formation, Nat Cell Biol, pp. 1019-1028, (2022)
  • [3] Batulan Z., Maarouf N., Shrivastava V., O'Brien E., Prophylactic salpingo-oophorectomy & surgical menopause for inherited risks of cancer: The need to identify biomarkers to assess the theoretical risk of premature coronary artery disease, Womens Midlife Health, (2018)
  • [4] Benincasa G., Suades R., Padro T., Badimon L., Napoli C., Bioinformatic platforms for clinical stratification of natural history of atherosclerotic cardiovascular diseases, European Heart Journal - Cardiovascular Pharmacotherapy, pp. 758-769, (2023)
  • [5] Bi X., Kuwano T., Lee P.C., Millar J.S., Li L., Shen Y., Et al., ILRUN, a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice, Circulation Research. Ovid Technologies, pp. 1347-1361, (2020)
  • [6] Bu T., Li Z., Hou Y., Sun W., Zhang R., Zhao L., Et al., Exosome-mediated delivery of inflammation-responsive Il-10 mRNA for controlled atherosclerosis treatment [Internet]., pp. 9988-10000
  • [7] Del Buono M.G., Moroni F., Montone R.A., Azzalini L., Sanna T., Abbate A., Ischemic Cardiomyopathy and Heart Failure After Acute Myocardial Infarction, Curr Cardiol Rep., pp. 1505-1515
  • [8] Butler A., Hoffman P., Smibert P., Papalexi E., Satija R., Integrating single-cell transcriptomic data across different conditions, technologies, and species, Nat Biotechnol, pp. 411-420
  • [9] Cai S., Zhao M., Zhou B., Yoshii A., Bugg D., Villet O., Et al., Mitochondrial dysfunction in macrophages promotes inflammation and suppresses repair after myocardial infarction, Journal of Clinical Investigation
  • [10] Chang S.-N., Chen J.-J., Wu J.-H., Chung Y.-T., Chen J.-W., Chiu C.-H., Et al., Association between Exosomal miRNAs and Coronary Artery Disease by Next-Generation Sequencing, Cells, (2021)
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