Project description:Mice were subjected to either isoprenaline (ISO, 30 mg/kg*d) or isoprenaline and phenylephrine (ISO/PE, 30 mg/kg*d each) for a period of 4 days via osmotic minipumps. At that timepoint, both ISO and ISO/PE treated animals showed a similar increase in heart weight to tibia length ratios. ECG-telemetry data collected from other individuals indicate a similar increase heart rate and normal blood pressure after 4 days of both ISO and ISO/PE exposure. Cardiac function was not assessed at that particular timepoint.
Project description:The first GSSM of V. vinifera was reconstructed (MODEL2408120001). Tissue-specific models for stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases.
Project description:Heart failure (HF) involves pathological cardiac remodeling, including cardiomyocyte loss and dysfunction. While the RNA-binding protein CPEB4 has been linked to cardiomyocyte activation, its role in HF remains unclear. We established in vivo and in vitro models of cardiac injury using isoproterenol (ISO). An HF mouse model was induced by chronic ISO administration (10 mg/kg/day, 3 weeks), while cellular injury was modeled by treating HL-1 cardiomyocytes with ISO (10 μM, 48 h). To investigate the molecular mechanisms, we employed transcriptome sequencing, qRT-PCR, and functional assays following siRNA-mediated knockdown of Cpeb4. Key endpoints included cell viability (CCK-8), apoptosis (Annexin V/7-AAD flow cytometry), and the alternative splicing of Eif4a2. In the HF mouse model, we observed significant cardiac hypertrophy and inflammatory infiltration, which correlated with a marked upregulation of Cpeb4 expression in cardiomyocytes. Notably, in vitro, siRNA-mediated knockdown of Cpeb4 significantly attenuated ISO-induced apoptosis and enhanced cell viability in HL-1 cells. Mechanistically, Cpeb4 depletion corrected the ISO-induced dysregulation of Eif4a2 alternative splicing, restoring the expression of its major isoforms and thereby ameliorating cellular injury. Our study identifies the Cpeb4-Eif4a2 axis as a key regulator in heart failure, with Cpeb4 driving cardiomyocyte apoptosis via aberrant Eif4a2 splicing, suggesting a promising therapeutic target.
Project description:Mechanical overload in the heart induces pathological remodeling that typcially leads to heart failure. We sought to build an in vitro model of heart failure by applying cyclic stretch to engineered isotropic (iso) and anisotropic (aniso) NRVM tissues. We used micoarrays to determine the effects of longitudinal and transvserse cyclic stretch on gene expression in engineered NRVM cardiac tissues. We found that cyclic stretch induced up-regulation of several known indicators of heart faliure, independent of the direction of stretch. NRVMs were seeded on silicone membranes coated with isotropic (iso) fibronectin (FN) or micropatterned with FN (aniso), cultured statically for 1h (t=0h), and stretched for increasing amount of time (t=6h, 24h, 96h) before RNA extraction and hybridization on Affymetrix microarrays. For aniso tissues, stretch was applied in either the longitudinal (long) or transverse (trans) direction. RNA was collected over six primary NRVM harvests and thus RNA was also extracted and analyzed from samples seeded for 1h (at t=0h) on iso FN to be used to normalize across cell harvests.