Carvedilol Suppresses Apoptosis and Ion Channel Remodelling of HL-1 Cardiac Myocytes Expressing E334K cMyBPC
R Endo1, U Bahrudin2, T Notsu2
1Department of Anesthesiology, Tottori University Faculty of Medicine, Yonago, Japan.
Insights
Carvedilol effectively suppresses cardiac cell apoptosis by altering apoptotic protein levels and increasing Cav1.2 expression, outperforming bisoprolol in protecting cells with E334K MyBPC mutations.
Area of Science:
- Cardiology
- Molecular Biology
- Cellular Biology
Background:
- Carvedilol exhibits antiarrhythmic and cardioprotective effects.
- Its impact on apoptosis and ion channel remodeling in specific cardiac cell models remains unclear.
Purpose of the Study:
- To investigate carvedilol's effects on apoptosis and ion channel remodeling in HL-1 cells with E334K MyBPC.
- To compare carvedilol's efficacy with that of bisoprolol.
Main Methods:
- Western blot and flow cytometry were used to analyze protein levels and apoptosis.
- HL-1 cells transfected with E334K MyBPC were treated with carvedilol and bisoprolol.
Main Results:
- Carvedilol reduced pro-apoptotic proteins (p53, Bax, cytochrome c) and increased anti-apoptotic Bcl-2.
- Bisoprolol did not alter these apoptotic markers.
- Both drugs increased Cav1.2 expression, but not Nav1.5.
- Carvedilol more effectively reduced annexin-V positive cells.
Conclusions:
- Carvedilol suppresses apoptosis in E334K MyBPC-expressing HL-1 cells via modulation of apoptotic proteins.
- This effect is linked to increased Cav1.2 protein expression.
Background:
Besides its antiarrhythmic action, carvedilol has an activity to suppress cardiac tissue damage. However, it is unknown whether it has any effect on cellular apoptosis and ion channel remodelling.
Purpose:
To know whether carvedilol has any effect on apoptosis and ion channel remodeling of HL-1 cells expressing E334K MyBPC, and comparing it with bisoprolol.
Method:
We examined effects of carvedilol and bisoprolol on the levels of pro- and anti-apoptotic proteins and ion channels as well as apoptosis of HL-1 cells transfected with E334K MyBPC using Western blot and flow cytometry.
Results:
Carvedilol decreased the protein levels of p53, Bax and cytochrome c and increased that of Bcl-2 in HL-1 cells expressing E334K MyBPC. Bisoprolol failed to affect the protein levels. Both carvedilol and bisoprolol increased the protein levels of Cav1.2 but not that of Nav1.5. Carvedilol was stronger than bisoprolol at decreasing the number of annexin-V positive cells in HL-1 cells expressing E334K MyBPC.
Conclusion:
Carvedilol suppressed apoptosis of HL-1 cells expressing E334K MyBPC through modification of pro- and anti-apoptotic proteins, whose was associated with an increase of Cav 1.2 protein expression.
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