Oxidative Stress and Pyroptosis in Doxorubicin-Induced Heart Failure and Atrial Fibrillation

Area of Science:

• Cardiology
• Oncology
• Molecular Biology

Background:

• Doxorubicin chemotherapy is associated with cardiotoxicity, including heart failure and atrial fibrillation.
• The TLR4/MyD88/NLRP3 pyroptosis pathway is implicated in heart failure and atherosclerosis.
• The role of oxidative stress and pyroptosis in doxorubicin-induced cardiotoxicity remains under-investigated.

Purpose of the Study:

• To investigate the role of oxidative stress and pyroptosis in doxorubicin-induced heart failure (HF) and atrial fibrillation (AF).
• To assess TLR4 expression and pyroptosis-associated proteins in patients undergoing doxorubicin chemotherapy.

Main Methods:

• Recruited 84 healthy subjects, 112 patients with Dox-induced HF, and 62 patients with Dox-induced AF.
• Measured mRNA and protein levels of TLR4, pyroptosis markers (cleaved caspase-1, NLRP3, GSDMD-N, HMGB-1), inflammatory factors, and oxidative stress.
• Samples collected at baseline and 3 months post-chemotherapy.

Main Results:

• Oxidative stress and pyroptosis markers increased from baseline to the Dox-HF group.
• No significant changes in oxidative stress or pyroptosis markers were observed after 3 months of Dox chemotherapy compared to baseline.
• Elevated oxidative stress and pyroptosis proteins correlate with cardiac systolic dysfunction.

Conclusions:

• Prolonged oxidative stress and pyroptosis contribute to doxorubicin-induced cardiac systolic dysfunction.
• TLR4 may serve as a novel biomarker for doxorubicin-induced heart failure.
• Targeting the TLR4 pathway presents a potential therapeutic strategy for mitigating doxorubicin cardiotoxicity.