Similar Datasets
Project description:The main adverse effect of tyrosine kinase inhibitors, such as sunitinib, is cardiac contractile dysfunction; however, the molecular mechanisms of this effect remain largely obscure. MicroRNAs (miRNAs) are key regulatory factors in both cardiovascular diseases and the tyrosine kinase pathway. Therefore, we analyzed the differential expression of miRNAs in the myocardium in mice after exposure to sunitinib using miRNA microarray. A significant downregulation of miR-146a was observed in the myocardium of sunitinib-treated mice, along with a 20% decrease in left ventricle ejection fraction (LVEF). The downregulation of miR-146a was further validated by RT-qPCR. Among the potential targets of miR-146a, we focused on Pln and Ank2, which are closely related to cardiac contractile dysfunction. Results of luciferase reporter assay confirmed that miR-146a directly targeted the 3' untranslated region of Pln and Ank2. Significant upregulation of PLN and ANK2 at the mRNA and protein levels was observed in the myocardium of sunitinib-treated mice. Cardiac-specific overexpression of miR-146a prevented the deteriorate effect of SNT on calcium transients, thereby alleviating the decreased contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). SiRNA knockdown of PLN or ANK2 prevented sunitinib-induced suppression of contractility in hiPSC-CMs. Therefore, our in vivo and in vitro results showed that sunitinib downregulated miR-146a, which contributes to cardiac contractile dysfunction by regulating the downstream targets PLN and ANK2, and that upregulation of miR-146a alleviated the inhibitory effect of SNT on cardiac contractility. Thus, miR-146a could be a useful protective agent against sunitinib-induced cardiac dysfunction.
| S-EPMC6716347 | biostudies-literature
Project description:MiR-146a downregulation contributes to sunitinib-induced cardiac dysfunction
| PRJNA518091 | ENA
Project description:Aim was to investigate the effect of cardiomyocyte-specific expression of the human Relaxin Family Peptide Receptor 1 (RXFP1) in a mouse model of pressure-overload induced cardiac dysfunction (TAC). Mice overexpressing the hRXFP1 receptor (or non-transgenic controls) underwent TAC (or Sham) surgery and were followed up for 8 weeks. Heart was removed and RNA isolated from left ventricle to perform bulk RNAseq.
2024-05-23 | GSE252607 | GEO
Project description:We employed the Affymetrix GeneChip technology to evaluate the patterns of expression in two different in vivo models of cardiac remodeling and in two different regions (left ventricle free wall and septum) of the heart. Mice underwent transverse aortic constriction (TAC); myocardial infarction (MI) or Sham operation and RNA from the left ventricle free wall and the septum was isolated 1 week later. Keywords: other
2003-08-22 | GSE415 | GEO
Project description:We employed the Affymetrix GeneChip technology to evaluate the patterns of expression in two different in vivo models of cardiac remodeling and in two different regions (left ventricle free wall and septum) of the heart. Mice underwent transverse aortic constriction (TAC); myocardial infarction (MI) or Sham operation and RNA from the left ventricle free wall and the septum was isolated 1 week later.
2007-12-13 | E-GEOD-415 | biostudies-arrayexpress
Project description:We tested the hypothesis that a set of differentially expressed genes could be used to predict cardiovascular phenotype in mice after prolonged catecholamine stress. Experiment Overall Design: We observed that WT FVB and B2KO mice developed systolic dysfunction in response to continuous catecholamine infusion while WT C57 mice developed diastolic dysfunction. Using these mice as the derivation cohort, we identified a set of 83 genes whose differential expression correlated with left ventricle systolic dysfunction. The gene set was then used to accurately predict development of left ventricle systolic dysfunction in a separate group of mice (WT B6129SF2/J) after catecholamine stress.
2009-10-26 | E-GEOD-12413 | biostudies-arrayexpress
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.
2011-12-21 | GSE27962 | GEO
Project description:Adult rabbit left ventricle RNAseq
| PRJNA475561 | ENA
Project description:Rationale: The lung-protective effects of dopamine and its role in the pathology of ventilator-induced lung injury (VILI) are emerging. However, the underlying mechanisms are still largely unknown. Objective: To investigate the contribution of dopamine receptor dysregulation in the pathogenesis of VILI and therapeutic potential of dopamine D1 receptor (DRD1) agonist in VILI. Methods: The role of dopamine receptors in mechanical stretch-induced endothelial barrier dysfunction and lung injury was studied in DRD1 knockout mice, in isolated mouse lung vascular endothelial cells (MLVECs), and in lung samples from patients who underwent pulmonary lobectomy with mechanical ventilation for different time periods. Measurements and Main Results: DRD1 was downregulated in both surgical patients and mice exposed to mechanical ventilation. Prophylactic administration of dopamine or DRD1 agonist attenuated mechanical stretch-induced lung endothelial barrier dysfunction and lung injury. By contrast, pulmonary knockdown or global knockout of DRD1 exacerbated these effects. Prophylactic administration of dopamine attenuated mechanical stretch-induced α-tubulin deacetylation and subsequent endothelial hyperpermeability through DRD1 signaling. We identified that cyclic stretch-induced glycogen-synthase-kinase-3β activation led to phosphorylation and activation of histone deacetylase 6 (HDAC6), which resulted in deacetylation of α-tubulin. Upon activation, DRD1 signaling attenuated mechanical stretch-induced α-tubulin deacetylation and subsequent lung endothelial barrier dysfunction through cAMP/exchange protein activated by cAMP (EPAC)-mediated inactivation of HDAC6. Conclusions: This work identifies a novel protective role for DRD1 against mechanical stretch-induced lung endothelial barrier dysfunction and lung injury. Further study of the mechanisms involving DRD1 in the regulation of microtubule stability and interference with DRD1/cAMP/EPAC/HDAC6 signaling may provide insight into therapeutic approaches for VILI.
| S-EPMC7806475 | biostudies-literature
Project description:Arterial pulmonary hypertension is a rare disease, with little knowledge regarding its etiology, and high mortality. Development of right and later on also left ventricular heart insufficiency, secondary to pulmonary hypertension, is a negative predictive factor. Genetic and molecular processes underlying left heart ventricle remodeling over the course of pulmonary hypertension remain unknown. In particular, there is no knowledge regarding the mechanisms of left heart ventricle atrophy which was completely avoided by researchers until recently.The aim of this study was to assess changes in protein abundance in left and right heart ventricle free wall of rats in monocrotaline model of PAH.
2020-09-07 | PXD015896 | Pride