(-)-Epicatechin protects against myocardial ischemia/reperfusion injury via autophagy-dependent ferroptosis

AIM: (-)-Epicatechin (EPI) has physiological activities such as antioxidant, anti-inflammatory and immune enhancement. In this study, we elucidated the protective effects of EPI in myocardial ischemia/reperfusion injury (MI/RI) and its mechanisms.

METHODS: An in vivo I/R model was constructed by performing left anterior descending coronary artery surgery on rats, and an in vitro I/R model was constructed by subjecting hypoxia/reperfusion treatment on H9C2 cells. The damage of cardiac tissues was detected by 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (H&E) staining, and expressions of ferroptosis-related proteins were examined by Western blot. Changes in the number of autophagosomes, the levels of oxidative stress and Fe2+ were also examined.

RESULTS: EPI reduced abnormal electrocardiogram waveform and infarct size caused by MI/RI in rats. The increasing trend of levels of reactive oxygen species (ROS) and Fe2+ was reversed by EPI, suggesting that EPI can reduce ferroptosis in vivo. Moreover, the levels of lipid ROS and LC3 in H9C2 cells were decreased with EPI treatment, and autophagy and ferroptosis were also alleviated in a dose-dependent manner in vitro. Co-cultivation of USP14 inhibitor IU1 and EPI further revealed that EPI regulates ferroptosis through the USP14-autophagy pathway.

CONCLUSIONS: EPI can reduce the level of oxidative stress by promoting USP14 to reduce autophagy, thus inhibiting autophagy dependent ferroptosis and reducing oxidative stress, and has a protective effect on myocardial infarction/myocardial infarction.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

Aging - 16(2024), 3 vom: 25. Jan., Seite 2181-2193

Sprache:

Englisch

Beteiligte Personen:

Junhong, Kong [VerfasserIn]
Yun, Tsai [VerfasserIn]
Guangxing, Shui [VerfasserIn]
Yuhan, Ding [VerfasserIn]
Qian, Xiang [VerfasserIn]
Haowen, Zhang [VerfasserIn]

Links:

Volltext

Themen:

(-)-Epicatechin
8R1V1STN48
Autophagy
Catechin
Ferroptosis
Journal Article
Myocardial ischemia reperfusion
ROS
Reactive Oxygen Species

Anmerkungen:

Date Completed 22.02.2024

Date Revised 06.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.18632/aging.205477

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36767629X