Enhanced MiR-711 transcription by PPARγ induces endoplasmic reticulum stress-mediated apoptosis targeting calnexin in rat cardiomyocytes after myocardial infarction.

MicroRNA 711 (miR-711) levels in the heart change dynamically after myocardial infarction (MI). As peroxisome proliferator-activated receptor gamma (PPARγ) can upregulate miR-711 in adipocytes and cardiac fibroblasts, this study examined the precise mechanism of PPARγ-mediated miR-711 upregulation and its role in the heart in the early stages after MI. In a rat model of MI induced by left anterior descending coronary artery ligation, immunohistochemical and western blot analyses revealed increased PPARγ expression in cardiomyocyte nuclei after MI. PPARγ modulated miR-711 levels in neonatal rat cardiomyocytes, and chromatin immunoprecipitation and luciferase assays revealed that it bound the premiR-711 promoter to upregulate miR-711. Bioinformatics analysis identified calnexin as a putative miR-711 target; this was confirmed by luciferase, western blot, and real-time polymerase chain reaction analyses. Additionally, the transfection of a miR-711 mimic into cardiomyocytes induced the endoplasmic reticulum (ER) stress-induced apoptosis response by upregulating glucose-regulated protein 78 (GRP78), activating transcription factor (ATF6), spliced X-box binding protein 1 (XBP1), apoptotic signal-regulating kinase 1 (ASK1), CCAAT-enhancer binding protein homologous protein (CHOP), caspase-12, and endoplasmic reticulum oxidoreductase 1 alpha (ERO1a). Similarly, on day 2 after MI, increased miR-711 levels in the heart were accompanied by increased cardiomyocyte apoptosis, decreased calnexin levels, and increased levels of GRP78, ATF6, spliced XBP1, ASK1, CHOP, and caspase-12, as well as cardiomyocytes apoptosis. The mechanism underlying these effects may involve the direct binding of PPARγ to the pre-miR-711 promoter for the upregulation of miR-711, which may induce ER stress-mediated cardiomyocyte apoptosis via calnexin. These findings augment the general knowledge of the post-MI pathological process and suggest a therapeutic strategy for cardiac remodelling in the early stages after MI.

Numerical Studies on Damage Behavior of Recycled Aggregate Concrete Based on a 3D Model.

This paper develops a 3D base force element method (BFEM) based on the potential energy principle. According to the BFEM, the stiffness matrix and node displacement of any eight-node hexahedral element are derived as a uniform expression. Moreover, this expression is explicitly expressed without a Gaussian integral. A 3D random numerical model of recycled aggregate concrete (RAC) is established. The randomness of aggregate was obtained by using the Monte Carlo random method. The effects of the recycled aggregate substitution and adhered mortar percentage on the elastic modulus and compressive strength are explored under uniaxial compression loading. In addition, the failure pattern is also studied. The obtained data show that the 3D BFEM is an efficient method to explore the failure mechanism of heterogeneous materials. The 3D random RAC model is feasible for characterizing the mesostructure of RAC. Both the substitution of recycled aggregate and the percentage of adhering mortar have a non-negligible influence on the mechanical properties of RAC. As the weak points in the specimen, the old interfacial transition zone (ITZ) and adhered mortar are the major factors that lead to the weakened properties of RAC. The first crack always appears in these weak zones, and then, due to the increase and transfer of stress, approximately two-to-three continuous cracks are formed in the 45°direction of the specimen.