Circ_005077 accelerates myocardial lipotoxicity induced by high-fat diet via CyPA/p47PHOX mediated ferroptosis
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View abstract on PubMed
Summary
This summary is machine-generated.High-fat diets induce heart problems by promoting myocardial lipotoxicity. Researchers discovered circ_005077, a circular RNA, exacerbates this condition by regulating ferroptosis, offering a potential therapeutic target.
Area Of Science
- Cardiovascular Biology
- Molecular Biology
- RNA Biology
Background
- Long-term high-fat diet (HFD) induces myocardial lipotoxicity, leading to cardiac dysfunction and heart failure.
- Circular RNAs (circRNAs) are implicated in cardiovascular diseases, but their role in myocardial lipotoxicity remains underexplored.
Purpose Of The Study
- To investigate the role and mechanism of circ_005077 in high-fat diet-induced myocardial lipotoxicity.
- To identify circ_005077 as a potential regulator of ferroptosis in the heart.
Main Methods
- Utilized high-fat diet (HFD) fed rats and palmitic acid (PA) treatment in vitro.
- Investigated the interaction of circ_005077 with Cyclophilin A (CyPA) and its effect on the ubiquitination proteasome system (UBS).
- Assessed the impact of circ_005077 on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and reactive oxygen species (ROS) generation.
Main Results
- Circ_005077 was significantly upregulated in the myocardium of HFD-fed rats.
- Circ_005077 acts as a ferroptosis regulator in palmitic acid (PA) and HFD-induced myocardial lipotoxicity.
- Circ_005077 inhibits CyPA degradation, promoting CyPA-p47phox interaction and enhancing NADPH oxidase activity, leading to ROS generation and ferroptosis.
Conclusions
- Circ_005077 plays a critical role in mediating myocardial lipotoxicity through ferroptosis.
- The circ_005077/CyPA/p47phox/NADPH oxidase axis is a key pathway in HFD-induced cardiac damage.
- Circ_005077 represents a potential therapeutic target for myocardial lipotoxicity associated with obesity and diabetes.
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