Meteorin­like/meteorin­ß protects against cardiac dysfunction after myocardial infarction in mice by inhibiting autophagy.

ABSTRACT

Meteorin-ß (Metrnß) 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 Metrnß 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)-Metrnß to overexpress Metrnß. 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-Metrnß to overexpress Metrnß, 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 Metrnß expression was reduced in both mouse serum and heart tissue 2 weeks post-MI. Metrnß overexpression using AAV9-Metrnß delivery reduced the mortality rate, decreased the infarction size and reduced the extent of myocardial injury 2 weeks post-MI. Furthermore, Metrnß overexpression inhibited cardiac hypertrophy, fibrosis and inflammation post-MI. In ischaemic H9c2 cells, Metrnß overexpression using adenovirus also reduced cell injury, cell death and inflammatory response. Metrnß overexpression suppressed MI-induced autophagy in vitro. Following autophagy activation using rapamycin in vitro, the protective effects induced by Metrnß were reversed. Taken together, these results indicated that Metrnß could protect against cardiac dysfunction post-MI in mice by inhibiting autophagy.