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:In vivo microRNA-target interactions from adult mouse cortex were identified with CLEAR-CLIP, a modified AGO HITS-CLIP approach that allows direct ligation of microRNA and target within purified, endogenous AGO-RNA complexes.
Project description:Heart failure is the final stage of various cardiovascular diseases, which seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including RNA binding protein RBFox2. It participates in regulation of cardiac function in multiple aspects and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures including mRNAs as well as miRNAs in the mouse model of heart failure after TAC surgery. Global and association analyses revealed that large-scale upregulation of miRNAs occurred at heart failure, which was not only responsible for degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBfox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBfox2 was targeted by multiple miRNAs including let-7, mir-16 and mir-208b, which were critical for cardiac function and upregulated in heart failure stage. Overexpression of these miRNAs suppressed rbfox2 protein and its downstream effects in cardiomyocytes, evidenced by suppressed alternative splicing of Enah gene and impaired E-C coupling via repression of Jph2 protein. Inhibition of let-7, the most abundant of these miRNAs in the heart, could rescue Rbfox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. These findings not only revealed the mechanism leading to RBFox2 depression in heart failure, but also provided an approach to rescue RBFox2 by miRNAs inhibition for the treatment of heart failure.
2023-01-25 | GSE215302 | GEO
Project description:RNA-Seq of mouse heart + ISO: anti-7oxo TG
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.
Project description:Transcriptomes performed on left ventricular heart samples from mice of the hybrid mouse diversity panel, a set of over a hundred inbred strains of mice. In this project, the strains were challenged with Isoproterenol, a beta-adrenergic agonist to induce cardiac hypertrophy and failure. Results are useful for the analysis of heart-related traits in mice Mice were given three weeks of ISO @ 20ug/g/day for three weeks, then sacrificed. Left ventricles from these mice and matched controls were used for transcripome analysis.
Project description:Heart failure is the final stage of various cardiovascular diseases, which seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including RNA binding protein RBFox2. It participates in regulation of cardiac function in multiple aspects and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures including mRNAs as well as miRNAs in the mouse model of heart failure after TAC surgery. Global and association analyses revealed that large-scale upregulation of miRNAs occurred at heart failure, which was not only responsible for degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBfox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBfox2 was targeted by multiple miRNAs including let-7, mir-16 and mir-208b, which were critical for cardiac function and upregulated in heart failure stage. Overexpression of these miRNAs suppressed rbfox2 protein and its downstream effects in cardiomyocytes, evidenced by suppressed alternative splicing of Enah gene and impaired E-C coupling via repression of Jph2 protein. Inhibition of let-7, the most abundant of these miRNAs in the heart, could rescue Rbfox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. These findings not only revealed the mechanism leading to RBFox2 depression in heart failure, but also provided an approach to rescue RBFox2 by miRNAs inhibition for the treatment of heart failure.
Project description:In order to study the changes of liver protein level in mice with acute cardiac rejection, we established a mouse model of ectopic heart transplantation. According to the matching relationship between recipient and donor, they were divided into the following two groups: allograft group (ALLO), BALB/ C hearts were transplanted into C57BL/6J recipients with complete mismatch of major histocompatibility complex; In the syngeneic transplantation group (ISO), C57BL/6J hearts were transplanted into MHC-matched C57BL/6J recipients. On day 6 after mouse heart transplantation, livers were obtained from recipient mice in the allograft group (n = 3) and from recipient mice in the syngeneic (ISO) group (n = 3). A series of techniques such as protein extraction, enzyme digestion, TMT labeling, HPLC classification, liquid chromatography-mass spectrometry tandem analysis, database search and bioinformation analysis were used to study the quantitative proteome of samples.