Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Physiology and Biophysics
First Advisor
Fadi Salloum
Second Advisor
Roland Pittman
Third Advisor
Frank Raucci
Fourth Advisor
Jose Huizar
Fifth Advisor
Stefano Toldo
Abstract
Duchenne muscular dystrophy (DMD) is the most prevalent and most severe form of muscular dystrophy in children. There is no cure for DMD, and the leading cause of death in patients with DMD is dilated cardiomyopathy (DCM). Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter that has shown promise as a cardioprotective agent. In this study, the potential role of H2S in the prevention of DCM was investigated in mdx4cv/mTRG2 mice, a ‘humanized’ mouse model of DMD. Early treatment with SG1002, a H2S prodrug, was effective in preserving cardiac function and also reducing progression of cardiac and skeletal muscle fibrosis in mdx4cv/mTRG2 mice. Mechanistic studies suggested that SG1002 may exert cardioprotective and musculoprotective effects by reducing the activity of the NLRP3 inflammasome and imparting an anti-inflammatory effect. Taken together, findings from this study indicate that SG1002, and therefore H2S, could serve as a novel therapeutic agent in DMD cardiomyopathy.
Rights
© 2024 Taylor Ine Roy
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-6-2024