Genome-wide analysis in PC6 electroacupuncture to ameliorate carfilzomib-induced cardiotoxicity in mice

Area of Science:

• Cardiovascular Research
• Integrative Medicine
• Molecular Biology

Background:

• Carfilzomib (CFZ), a proteasome inhibitor for multiple myeloma (MM), causes cardiotoxicity, limiting its use.
• Proteasome inhibitor-induced cardiotoxicity is a significant clinical challenge.
• Electroacupuncture (EA) is explored as a potential cardioprotective therapy.

Purpose of the Study:

• To investigate the cardioprotective effects of EA at the Neiguan acupoint (PC6) against CFZ-induced cardiotoxicity.
• To elucidate the molecular mechanisms underlying EA's therapeutic effects using transcriptomic analysis.
• To identify key genes and pathways involved in mitigating CFZ-induced cardiac damage.

Main Methods:

• Mice were treated with DMSO (control), CFZ, or EA at PC6 after CFZ administration.
• Comparative transcriptomic profiling of heart tissues was performed.
• Differentially expressed genes (DEGs) were identified and analyzed using Metascape.
• Key gene expression was validated using quantitative real-time PCR (RT-qPCR).

Main Results:

• EA reversed CFZ-induced reductions in ejection fraction and fractional shortening.
• Transcriptomic analysis identified 770 DEGs in the CFZ group and 329 DEGs in the EA group.
• Co-expressed DEGs were enriched in pathways related to muscle contraction and skeletal system development.
• Expression patterns of specific genes (e.g., Myl4, Col1a1) were confirmed by RT-qPCR.

Conclusions:

• PC6-based EA therapy demonstrates significant cardioprotective effects against CFZ-induced cardiotoxicity.
• EA modulates specific gene expression profiles, offering insights into its therapeutic mechanisms.
• This study provides a theoretical basis for utilizing EA in managing cardiotoxicity in MM patients.