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Published on: June 29, 2022
Cardamonin inhibits atrial remodeling in mice by upregulating the expression of USP18
Zhenyu Feng1, Yiheng Yang1, Wenjun Zheng2
1Institute of Cardiovascular Diseases, The first affiliated Hospital of Dalian Medical University, Dalian, , People's Republic of China.
Insights
Cardamonin, a natural compound, effectively treats atrial remodeling and fibrillation by regulating USP18. This discovery offers new therapeutic strategies for cardiovascular diseases.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Molecular Biology
Background:
- Atrial remodeling is the primary driver of atrial fibrillation.
- Cardamonin, derived from traditional Chinese medicine, shows potential benefits for heart health.
- The specific mechanisms of Cardamonin's effects on atrial remodeling require further investigation.
Purpose of the Study:
- To investigate the effects of Cardamonin on atrial remodeling and atrial fibrillation.
- To elucidate the role of USP18 in Cardamonin's therapeutic actions.
- To explore the molecular pathways linking Cardamonin, USP18, and atrial remodeling.
Main Methods:
- Angiotensin II (Ang II) was used to induce atrial fibrillation in mice.
- Cardamonin was administered at various doses.
- Adeno-associated virus serotype 9 (AAV9) mediated overexpression of USP18 and myocardial-specific knockout of USP18 were performed.
- Echocardiography, electrical stimulation, qPCR, and pathological staining were employed.
- Molecular biology experiments were conducted to determine the relationship between Cardamonin and USP18.
Main Results:
- Cardamonin reduced the incidence and duration of Ang II-induced atrial fibrillation, alongside decreased atrial fibrosis, inflammation, and oxidative stress.
- USP18 overexpression enhanced Cardamonin's protective effects against atrial fibrillation and remodeling.
- USP18 knockout diminished Cardamonin's anti-remodeling efficacy.
- Cardamonin's anti-atrial remodeling effect was comparable to amiodarone.
- Cardamonin may regulate USP18 transcription via NRF2 binding, and USP18 may interact with SERCA2.
Conclusions:
- Cardamonin regulates atrial remodeling through the USP18 pathway.
- These findings provide a theoretical basis for developing novel, safe therapeutics for atrial remodeling.
- This research opens new avenues for treating cardiovascular diseases with improved efficacy and safety.
Background:
Atrial fibrillation is primarily driven by atrial remodeling. Cardamonin, extracted from ancient Chinese remedies, has a beneficial effect on heart health. However, it is still needed to investigate the specific effects of Cardamonin on atrial remodeling.
Methods:
We utilized Ang II to induce atrial fibrillation. Different doses of Cardamonin were administered to mice. AAV9-cTNT-USP18 and myocardial-specific knockout of USP18 were constructed. Through echocardiography, electrical stimulation, qPCR and pathological staining, the roles of CAR and USP18 in atrial remodeling were demonstrated. amiodarone was the positive control for observing the anti- atrial fibrillation effects of CAR. The indirect relationship between CAR and USP18 was found by various molecular biology experiments RESULTS: The findings indicated that Cardamonin effectively decreased the occurrence and duration of AF induced by Ang II, as well as lowered levels of atrial fibrosis, inflammation, and oxidative stress. Overexpression of USP18 could promote the inhibitory effect of Cardamonin on Ang II-induced incidence and duration of AF, and significantly suppressing atrial remodeling in mice. In contrast, knockout of USP18 significantly interfered with the anti-atrial remodeling effect of Cardamonin, increasing atrial remodeling. The anti-remodeling effect of CAR on the atrium is comparable to that of amiodarone. At the same time, it was found that CAR may bind to NRF2 to regulate the transcription level of USP18. USP18 may interact with SERCA2.
Conclusions:
These results not only clarify that Cardamonin regulates atrial remodeling through USP18, but also provide a theoretical basis for the development of new and safe therapeutic drugs for atrial remodeling, opening up new avenues for the treatment of cardiovascular diseases and bringing hope for more effective and safer treatment options.
