Electroacupuncture at PC6 Acupoint Adjusts Genome-Wide Gene Expressions and Alters Carfilzomib-Induced Cardiotoxicity in Mice

Carfilzomib (CFZ) is a proteasome inhibitor commonly used in the treatment of multiple myeloma, but its clinical application is limited due to its cardiotoxicity. The Neiguan acupoint (PC6) stimulation has been reported to effectively improve cardiac function, but its regulatory mechanism remains unclear. The aim of this study was to investigate the effect and underlying mechanism of electroacupuncture (EA) against CFZ-induced cardiotoxicity in C57BL/6 mice. According to our results, EA treatment significantly reversed CFZ-induced ejection fraction and fractional shortening reduction, which showed great potential effect for heart protection. By using RNA-sequencing, we compared the transcriptome profile of heart samples from DMSO control, CFZ injection, and EA treatment mice, and nearly 40,000,000 valid sequence reads aligned with 20,000 genes from six libraries were obtained. A total of 770 differentially expressed genes (DEGs) were identified in the CFZ (vs. Control) group, including 65 up-regulated and 705 down-regulated genes. Meanwhile, 329 DEGs were obtained in the EA (vs. CFZ) group, including 251 up-regulated and 78 down-regulated genes. Our results shed new insights into the regulatory mechanism of EA at PC6 against CFZ-induced cardiotoxicity, which could further provide theoretical basis for clinical EA therapy. Overall design: The transcriptome profiles of heart samples from DMSO control, CFZ injection, and EA treatment mice were generated in duplicate, using Illumina NovaSeq 6000.