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EVA1A (Eva-1 homologue A) is a novel lysosome and endoplasmic reticulum-associated protein that can regulate cell autophagy and apoptosis. Eva1a is expressed in the myocardium, but its function in myocytes has not yet been investigated. Therefore, we generated inducible, cardiomyocyte-specific Eva1a knockout mice with an aim to determine the role of Eva1a in cardiac remodelling in the adult heart. Data from experiments showed that loss of Eva1a in the adult heart increased cardiac fibrosis, promoted cardiac hypertrophy, and led to cardiomyopathy and death. Further investigation suggested that this effect was associated with impaired autophagy and increased apoptosis in Eva1a knockout hearts. Moreover, knockout of Eva1a activated Mtor signalling and the subsequent inhibition of autophagy. In addition, Eva1a knockout hearts showed disorganized sarcomere structure and mitochondrial misalignment and aggregation, leading to the lack of ATP generation. Collectively, these data demonstrated that Eva1a improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing autophagy. In conclusion, our results demonstrated that Eva1a may have an important role in maintaining cardiac homeostasis.

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The aim of the present study was to investigate the association of the serum angiopoietin (Ang)-1 and Ang-2 levels and the Ang-2 to Ang-1 ratio (Ang-2/Ang-1) with heart failure (HF) in patients with acute myocardial infarction (AMI) during hospitalization. The serum Ang-1 and Ang-2 levels of the AMI patients were measured at admission to hospital. The correlations between serum Ang-1, Ang-2 and Ang-2/Ang-1 with HF were examined. Among 103 patients, 20 developed HF during hospitalization. The serum Ang-2 level and Ang-2/Ang-1 were found to be significantly higher in the patients with HF than in the patients without HF (2,203.1±122.0 vs. 2,102.3±114.4 pg/ml, P=0.001 and 11.4±1.6×10−2 vs. 10.6±1.1×10−2, P=0.007, respectively). Serum Ang-2 level and Ang-2/Ang-1 were negatively correlated with left ventricular ejection fraction (LVEF; r=−0.352, P<0.001 and r=−0.365, P<0.001, respectively) and positively correlated with the natural logarithm of the level of N-terminal pro-B-type natriuretic peptide (LnNT-proBNP, r=0.367, P<0.001 and r=0.304, P=0.003, respectively) and peak cardiac troponin T (cTnT, r=0.421, P<0.001 and r=0.278, P=0.009, respectively). However, the serum Ang-1 level was not found to correlate significantly with LVEF (r= 0.194, P= 0.05), LnNT-proBNP (r=−0.116, P=0.266) or peak cTnT (r=−0.056, P=0.607). In multivariable logistic regression analysis, Ang-2 (P=0.031), Ang-2/Ang-1 (P=0.018) and NT-proBNP (P=0.001) were revealed to be independently associated with HF. The present study reveals that Ang-2 levels and Ang-2/Ang-1 are independent predictors of HF in AMI patients during hospitalization.

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Acute liver failure (ALF) is an inflammation-mediated hepatocellular injury process associated with cellular autophagy. However, the mechanism by which autophagy regulates ALF remains undefined. Herein, we demonstrated that Eva1a (eva-1 homolog A)/Tmem166 (transmembrane protein 166), an autophagy-related gene, can protect mice from ALF induced by d-galactosamine (D-GalN)/lipopolysaccharide (LPS) via autophagy. Our findings indicate that a hepatocyte-specific deletion of Eva1a aggravated hepatic injury in ALF mice, as evidenced by increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), myeloperoxidase (MPO), and inflammatory cytokines (e.g., TNFα and IL-6), which was associated with disordered liver architecture exhibited by Eva1a−/− mouse livers with ALF. Moreover, we found that the decreased autophagy in Eva1a−/− mouse liver resulted in the substantial accumulation of swollen mitochondria in ALF, resulting in a lack of ATP generation, and consequently hepatocyte apoptosis or death. The administration of Adeno-Associated Virus Eva1a (AAV-Eva1a) or antophagy-inducer rapamycin increased autophagy and provided protection against liver injury in Eva1a−/− mice with ALF, suggesting that defective autophagy is a significant mechanism of ALF in mice. Collectively, for the first time, we have demonstrated that Eva1a-mediated autophagy ameliorated liver injury in mice with ALF by attenuating inflammatory responses and apoptosis, indicating a potential therapeutic application for ALF.