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- Title
Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation.
- Authors
Mathis, Bryan J.; Kato, Hideyuki; Hiramatsu, Yuji
- Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the endogenous antioxidant response to reactive oxygen species as well as a controller of Phase II detoxification in response to xenobiotics. This amenity to specific external manipulation exploits the binding affinity of Nrf2 for its constitutive repressor and degradation facilitator Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1). Derived from both natural and synthesized origins, these compounds have been extensively tested without definitive beneficial results. Unfortunately, multiple terminated trials have shown a negative side to Nrf2 with regard to cardiac pathologies while animal-based studies have demonstrated cardiomyocyte hypertrophy and heart failure after chronic Nrf2 upregulation. Putatively based on autophagic control of Nrf2 activity-modulating upstream factors, new evidence of miRNA involvement has added complexity to this mechanism. What follows is an extensive survey of Nrf2-regulating exogenous compounds that may promote cardiomyopathy, clinical trial evidence, and a comparison to exercise-induced factors that also upregulate Nrf2 while preventing cardiac pathologies.
- Subjects
NUCLEAR factor E2 related factor; CARDIAC hypertrophy
- Publication
Cells (2073-4409), 2022, Vol 11, Issue 23, p3855
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells11233855