Cardiac reprogramming via transient overexpression of P-glycoprotein alleviates doxorubicin-induced cardiotoxicity in mice and pigs - PubMed
2 hours ago
- #P-glycoprotein
- #doxorubicin-induced cardiotoxicity
- #cardiac reprogramming
- Cardiac reprogramming via transient P-glycoprotein (P-gp) overexpression reduces doxorubicin-induced cardiotoxicity by lowering intracellular doxorubicin levels in cardiomyocytes.
- The strategy uses lipid nanoparticle-based mRNA therapeutics to temporarily overexpress P-gp, inspired by cancer drug resistance mechanisms.
- In mouse models, this approach improves survival, restores cardiac function, and reduces myocardial fibrosis and structural changes.
- In male pig models, intrapericardial injection of P-gp mRNA lipid nanoparticles effectively mitigates adverse effects and restores cardiac function.
- The method demonstrates safety, efficacy, and clinical potential for alleviating chemotherapy-related cardiotoxicity.