ABSTRACT: Neuregulin-1 (NRG-1) is a paracrine factor critical for cardiac development. We have been examining whether the recombinant NRG-1β isoform known as glial growth factor 2 (GGF2) has therapeutic potential for heart failure. In both small and large animals after experimental myocardial infarction (MI) we have found that GGF2 treatment improves myocardial function and limits progressive myocardial remodeling. To understand potential mechanisms for this effect, we compared gene expression in swine by microarray analysis. We used microarrays to compared th the global gene expression underlying the efficacy of GGF2 treatment for heart injury. Left ventricular tissue remote from the site of infarct was collected from each of 8 animals (3 untreated controls, 3 low dose GGF2-treated and 2 high dose GGF2-treated) and processed for gene expression microarray analysis using Affymetrix porcine genome GeneChips.
Project description:Neuregulin-1 (NRG-1) is a paracrine factor critical for cardiac development. We have been examining whether the recombinant NRG-1β isoform known as glial growth factor 2 (GGF2) has therapeutic potential for heart failure. In both small and large animals after experimental myocardial infarction (MI) we have found that GGF2 treatment improves myocardial function and limits progressive myocardial remodeling. To understand potential mechanisms for this effect, we compared gene expression in swine by microarray analysis. We used microarrays to compared th the global gene expression underlying the efficacy of GGF2 treatment for heart injury.
Project description:The molecular mechanism underlying cardiac remodeling following myocardial infarction have been incompletely understood. Until now, most studies have been performed in rodents. We studied cardiac remodeling in the physiologically more relevant animal model, the swine. Microarray analysis was performed on animals that underwent either sham surgery or permanent ligation of the left coronary artery (MI). RNA was isolated from the remote, non-ischemic, regions of the left ventricle. RNA was isolated from 8 sham and 8 MI animals three weeks after surgery. Each group contained 4 males and 4 females. Animals used for the study were 2-3 months old Yorkshire x Landrace swine. Only neutered males entered the study.
Project description:In this study, we used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted cardiomyocyte proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing cardiomyocyte apoptosis. Rather, we found that AAV9:hYAP stimulated adult cardiomyocyte proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated cell cycle gene expression, enhanced TGFβ-signaling, and activated of components of the inflammatory response.Cardiac specific YAP activation after MI mitigated myocardial injury after MI, improved cardiac function and mouse survival. These findings suggest that therapeutic activation of hYAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI. Three groups were involved in this study: sham group, AAV9:Luci+MI group and AAV9-YAP+MI group. Each group contained three biological replicates. The sham group had neither myocardial infarction nor AAV injection. The AAV9:Luci +MI(L for brief) group had myocardial infarction and injected with AAV9:Luic. The AAV9:hYAP+MI(YAP for brief) group had myocardial infarction and injected with AAV9:hYAP. 5 days after MI and AAV injection, the heart apexes were collected and the total RNA were isolated for microarray analysis.
Project description:Exogenous glucocorticoids interact with the circadian clock, but little attention is paid to their time of intake. Here we investigated the transcriptional effects of prednisone in heart when pulsed as intermittent once-weekly 1mg/kg i.p. dose in WT mice at ZT0 at 2-weeks after sham or myocardial infarction (MI; permanent ligation) surgeries. Aftter 6 weeks of treatment, we performed RNA-seq analysis in myocardial tissue to quantitate gene expression at isoform level.
Project description:Cardiac fibrosis is a common feature of ischemic heart disease and cardiac fibroblasts (CF) are key players in cardiac remodeling of the injured heart after myocardial infarction (MI). Fibrosis increases myocardial stiffness, thereby impairing cardiac function, which ultimately progresses to end-stage heart failure. Little is known, however, on the secretome of CF and cell-to-cell communication of CF is only incompletely understood. Here, we in vivo labeled secreted proteins by expressing TurboID under control of the POSTN promotor in cardiac fibroblasts of mouse with myocardial infarction, enriched biotinylated proteins and analyzed them using LC-MS.
Project description:We systematically identified, annotated and characterised the mouse long non-coding transcriptome during myocardial infarction, revealing hundreds of novel heart specific lncRNAs with unique functional and regulatory characteristics. 2 conditions, 4 biological replicates per condition
Project description:It remains unclear how sleep influences inflammatory pathways after myocardial infarction (SF). In this study, we relied on established murine models and assessed how sleep fragmentation (SF) alters transcriptional programing in the blood, heart, and brain after MI.
Project description:We systematically identified, annotated and characterised the mouse long non-coding transcriptome during myocardial infarction, revealing hundreds of novel heart specific lncRNAs with unique functional and regulatory characteristics.
Project description:Nowadays, sepsis and septic shock have become major public health problems, which are the main cause of death among patients admitted to the intensive care units. Notably, myocardial dysfunction during sepsis, usually called sepsis-induced myocardial depression, is common in septic shock patients whose incidence is about 70% and leads to a high mortality. However, the mechanism underlying the septic myocardial depression is still unclear. Recently, proteomics has become a powerful method for explore protein dynamics and their complex regulatory mechanism, and thus generates a profound impact on precision medicine and the clinical setting. Importantly, the expression patterns of global proteins in heart tissue between sepsis and control group remain unclear. Therefore, we performed the rat models of sepsis-induced myocardial depression and investigated global protein expression profiles in heart tissue between sepsis and control group using 4D label-free proteomic technique.
Project description:To investigate the role of Nrg-1 in heart ventricular chamber development we deleted Nrg-1 in endothelial lineages, harvested hearts at E9.5, and determined gene expression profiles, using RNA-seq.