Meteorin‑like/meteorin‑&beta; protects against cardiac dysfunction after myocardial infarction in mice by inhibiting autophagy

Shangguan,Jiahong; Liu,Gangqiong; Xiao,Lili; Zhang,Wenjing; Zhu,Xiaodan; Li,Ling

doi:10.3892/etm.2024.12582

Meteorin‑like/meteorin‑β protects against cardiac dysfunction after myocardial infarction in mice by inhibiting autophagy

Authors:
- Jiahong Shangguan
- Gangqiong Liu
- Lili Xiao
- Wenjing Zhang
- Xiaodan Zhu
- Ling Li
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: May 22, 2024 https://doi.org/10.3892/etm.2024.12582
Article Number: 293
Copyright: © Shangguan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Meteorin‑β (Metrnβ) is a protein that is secreted by skeletal muscle and adipose tissue, and participates in cardiovascular diseases. However, its role in myocardial infarction (MI) has not been fully elucidated to date. The aim of the present study was to investigate the role and underlying mechanism of Metrnβ in MI. In the present study, mice were subjected to left coronary ligation to induce a MI model before being injected with adeno‑associated virus 9 (AAV9)‑Metrnβ to overexpress Metrnβ. Mice were subjected to echocardiography and pressure‑volume measurements 2 weeks after ligation. Cardiac injury was measured from the levels of cardiac troponin T and pro‑inflammatory factors, which were detected using ELISA kits. Cardiac remodelling was determined from the cross‑sectional areas detected using H&E and wheat germ agglutinin staining as well as from the transcriptional levels of hypertrophic and fibrosis markers detected using reverse transcription‑quantitative PCR. Cardiac function was detected using echocardiography and pressure‑volume measurements. In addition, H9c2 cardiomyocytes were transfected with Ad‑Metrnβ to overexpress Metrnβ, before being exposed to hypoxia to induce ischaemic injury. Apoptosis was determined using TUNEL staining and caspase 3 activity. Cell inflammation was detected using ELISA assays for pro‑inflammatory factors. Autophagy was detected using LC3 staining and assessing the protein level of LC3II using western blotting. H9c2 cells were also treated with rapamycin to induce autophagy. It was revealed that Metrnβ expression was reduced in both mouse serum and heart tissue 2 weeks post‑MI. Metrnβ overexpression using AAV9‑Metrnβ delivery reduced the mortality rate, decreased the infarction size and reduced the extent of myocardial injury 2 weeks post‑MI. Furthermore, Metrnβ overexpression inhibited cardiac hypertrophy, fibrosis and inflammation post‑MI. In ischaemic H9c2 cells, Metrnβ overexpression using adenovirus also reduced cell injury, cell death and inflammatory response. Metrnβ overexpression suppressed MI‑induced autophagy in vitro. Following autophagy activation using rapamycin in vitro, the protective effects induced by Metrnβ were reversed. Taken together, these results indicated that Metrnβ could protect against cardiac dysfunction post‑MI in mice by inhibiting autophagy.

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