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American Heart Association

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Final ID: P-396

A Selective Agonist of the Beta 2 Retinoic Acid Receptor Reduces Necrosis, Lipid Peroxidation, and Oxidative Stress in Doxorubicin-induced Cardiotoxicity

Abstract Body: Objective: Doxorubicin (Doxo) is used as an antiproliferative agent to treat various cancers. However, a significant limitation of Doxo is cardiotoxicity, that can induce heart failure in patients. Mounting evidence indicates that an increased generation of reactive oxygen species (ROS), lipid peroxidation, and necrosis, are major causes of Doxo-induced heart failure. Recently, we reported that a highly selective and potent agonist of the b2 retinoic acid receptor (RARb2), improved cardiac dysfunction in mice model of myocardial infarction by inhibiting oxidative stress. In this study we investigated cardioprotective effects of RARb2 stimulation on Doxo-induced heart failure. Methods: We performed in vitro and in vivo experiments on an established murine model of Doxo-induced heart failure. Necrosis, oxidative stress, and lipid peroxidation were evaluated, assessing both the prevention and the rescue capacities of RARb2 stimulation. Results: An increased ROS production both at the mitochondrial and cellular level was observed in cardiomyocytes isolated from Doxo-treated mice. RARb2 stimulation significantly attenuated Doxo-induced ROS production. In addition, this treatment mitigated lipid peroxidation induced by Doxo in the left ventricle, marked by 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). RARb2 stimulation also mitigated the increased expression of High Mobility Group Box 1 (HMGB1), a necrosis marker, in the heart and in the serum of Doxo-treated mice. Conclusion: Our data demonstrate that RARb2 stimulation can attenuate necrosis, lipid peroxidation, and ROS production in a mouse model of Doxo cardiotoxicity.
  • Varzideh, Fahimeh  ( Albert Einstein College of Medicine , Bronx , New York , United States )
  • Jankauskas, Stanislovas  ( Albert Einstein College of Medicine , Bronx , New York , United States )
  • Kansakar, Urna  ( Albert Einstein College of Medicine , Bronx , New York , United States )
  • Tang, Xiao-han  ( Weill Cornell Medicine , New York , New York , United States )
  • Gudas, Lorraine  ( Weill Cornell Medicine , New York , New York , United States )
  • Levi, Roberto  ( Weill Cornell Medicine , New York , New York , United States )
  • Gambardella, Jessica  ( Albert Einstein College of Medicine , Bronx , New York , United States )
  • Santulli, Gaetano  ( Albert Einstein College of Medicine , Bronx , New York , United States )
  • Author Disclosures:
    Fahimeh Varzideh: DO NOT have relevant financial relationships | Stanislovas Jankauskas: No Answer | Urna Kansakar: DO NOT have relevant financial relationships | Xiao-Han Tang: No Answer | Lorraine Gudas: No Answer | Roberto Levi: DO NOT have relevant financial relationships | Jessica Gambardella: No Answer | Gaetano Santulli: DO NOT have relevant financial relationships
Meeting Info:
Session Info:

Poster Session 2

Friday, 09/06/2024 , 09:00AM - 10:30AM

Poster Session

More abstracts from these authors:
The Dual Endothelin-1 Antagonist Aprocitentan Attenuates Mitochondrial Oxidative Stress in Human Cardiac Fibroblasts

Varzideh Fahimeh, Jankauskas Stanislovas, Densu Agyapong Esther, Kansakar Urna, Santulli Gaetano

Inhibition of Inositol 1,4,5-trisphosphate receptors (ITP3Rs) in Cardiac Myofibroblasts Attenuates Post-Ischemic Cardiac Fibrosis

Kansakar Urna, Varzideh Fahimeh, Wang Xujun, Santulli Gaetano, Jankauskas Stanislovas

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