Angiotension II directly bind P2X7 receptor to induce myocardial ferroptosis and remodeling by activating human antigen R
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View abstract on PubMed
Summary
This summary is machine-generated.Targeting the P2X7 receptor (P2X7R) may treat heart failure. Blocking P2X7R reduces ferroptosis and cardiac remodeling caused by angiotensin II (Ang II).
Area Of Science
- Cardiology
- Molecular Biology
- Pathophysiology
Background
- Cardiac remodeling can lead to heart failure, with ferroptosis implicated in its development.
- The P2X7 receptor (P2X7R) is increasingly recognized for its role in cardiovascular diseases.
Purpose Of The Study
- To investigate the interaction between P2X7R and ferroptosis in angiotensin II (Ang II)-induced cardiac remodeling.
- To explore the therapeutic potential of targeting P2X7R in hypertensive heart failure.
Main Methods
- Utilized P2X7R knockout mice to study cardiac remodeling and ferroptosis.
- Employed molecular biological techniques to elucidate the underlying mechanisms.
- Investigated the direct interaction between Ang II and P2X7R, including specific binding sites.
Main Results
- Ferroptosis is a key mediator of Ang II-induced cardiac remodeling.
- P2X7R deficiency significantly attenuated cardiac dysfunction, remodeling, and ferroptosis.
- Ang II directly binds to P2X7R, involving specific amino acid residues (LYS-66, MET-212).
- P2X7R blockade altered HuR shuttling and expression, impacting GPX4 and HO-1 mRNA stability.
Conclusions
- P2X7R plays a critical role in ferroptosis during Ang II-induced cardiac remodeling.
- Targeting P2X7R represents a potential therapeutic strategy for managing ferroptosis-related cardiac dysfunction and hypertensive heart failure.
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