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PROVIDER: PRJNA607974 | ENA |
REPOSITORIES: ENA
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Project description:Genomic expression patterns of mitral valve tissues from dogs with degenerative mitral valve disease
| PRJNA106375 | ENA
Project description:We here report the results of a mitral valve transcriptome study designed to identify genes and molecular pathways involved in development of congestive heart failure (CHF) following myxomatous mitral valve disease (MMVD) in dogs. The study is focused on a cohort of elderly age-matched dogs (n=34, age ~10 years) from a single breed – Cavalier King Charles Spaniels (CKCS) – with a high incidence of MMVD. The cohort comprises 19 dogs (10♀, 9♂) without MMVD-associated CHF, and 15 dogs (6♀, 9♂) with CHF caused by MMVD. I.e. we compare gene expression in breed and age matched groups of dogs, which only differ with respect to CHF status. We identify 56 genes, which are differentially expressed between the two groups. In this list of genes, we confirm an enrichment of genes related to the TNFβ signaling pathway, extracellular matrix organization, vascular development, and endothelium damage, which also have been identified in previous studies. However, the genes with the greatest difference in expression between the two groups are CNTN3 and MYH1. Both genes encode proteins, which are predicted to have an effect on the contractile activity of myocardial cells, which in turn may have an effect on valvular performance and hemodynamics across the mitral valve. This may result in shear forces with impact on MMVD progression.
2023-11-10 | GSE217750 | GEO
Project description:In this study, we aimed to demonstrate expression profiles of circulating microRNAs (miRNAs) in dogs with eccentric or concentric cardiac hypertrophy, and investigate whether there is a difference in miRNA expression according to the type of cardiac hypertrophy. Dogs with myxomatous mitral valve degeneration (MMVD) or pulmonic stenosis (PS) were included in this study, which are the two representative diseases of eccentric or concentric cardiac hypertrophy in dogs, respectively. Circulating miRNAs were isolated from the serum samples of five dogs with MMVD, five dogs with PS, and five healthy dogs. The circulating miRNA expression levels of dogs with MMVD or PS were compared with those of the healthy dogs by microarray analysis (Affymetrix GeneChip miRNA 4.0), using two independent parameters, a fold change cut-off of > 1.5 (up or down regulation) and p-value of < 0.05.
2021-03-24 | E-MTAB-10029 | biostudies-arrayexpress
Project description:Development and progression of myxomatous mitral valve disease (MMVD) in domestic dogs is unpredictable and pathobiology still unclear. The American College of Veterinary Internal Medicine (ACVIM) perceived that mayor improvement in management of diseased dogs would be timely diagnosis, especially detection of transition from MMVD stage B1 into B2. Thus, in this study we compared by tandem mass tag (TMT) protocol and mass spectrometry (MS) acquired quantitative proteome profiles of serum collected from healthy (control) (N=12) and dogs diagnosed with different stages of naturally occurring MMVD: B1 (N=13), B2 (N=12) and C (N=13). Prior to proteomic analysis dogs were distinguished into experimental categories based on echocardiography results. Serum biochemistry and concentrations of three cardiac biomarkers (galectin-3, suppression of tumorigenicity 2 and asymmetric dimethylarginine) were performed to obtain better characterization of healthy/control group and MMVD cases.
2023-05-10 | PXD038475 | Pride
Project description:Degenerative mitral valve disease (DMVD) is the most common cardiac disease in dogs. Some signaling pathways have been implicated in DMVD, including the serotonin and TGF-beta pathways. We sought to identify additional molecular and metabolic pathways that contribute to DMVD using transcriptomic and metabolomic studies. RNA-seq gene expression evaluated on total RNA isolated from left ventricle (LV) and mitral valve (MV) identified 812 differentially expressed transcripts (DETs) in LV and 263 DETs in MV. Out of 15 transcripts selected for RT-qPCR validation, we confirmed 13. In addition, serum samples were collected for metabolomic evaluation. Endothelial nitric oxide synthase (eNOS) was significantly up-regulated in both LV and MV while the level of circulating asymmetrical dimethyl arginine (ADMA), an endogenous NOS inhibitor, was lower in DMVD. Expressions of matrix metalloproteinases (MMP) and their endogenous inhibitor tissue inhibitor of matrix metallopeptidases (TIMP) were altered. This study demonstrates transcript and metabolite differences consistent with increased nitric oxide (NO) and reactive oxygen species (ROS) production, impaired fatty acid transport and oxidation, and increased glucose uptake and glycolysis in DMVD. Our findings are consistent with metabolic conversion in the DMVD heart from oxidative metabolism to glycolysis along with an increased concentration of NO and ROS activity suggesting an alternative signaling effect. Alterations of redox-sensitive NO signaling may play a role in ECM (ECM) homeostasis via modulating MMP and TIMP expression.
2015-05-29 | GSE64544 | GEO
Project description:Exploring the mechanisms of valvular heart disease (VHD) at the cellular level may be useful to identify new therapeutic targets; however, the comprehensive cellular landscape of non-diseased human cardiac valve leaflets remains unclear. The cellular landscapes of non-diseased human cardiac valve leaflets (five aortic valves, five pulmonary valves, five tricuspid valves, and three mitral valves) from end-stage heart failure patients undergoing heart transplantation were explored using single-cell RNA sequencing (scRNA-seq)
2022-09-13 | GSE213128 | GEO
Project description:Pulmonary hypertension (PH), a common complication in dogs affected by degenerative mitral valve disease (DMVD), is a progressive disorder characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular remodeling. Early diagnosis of PH is crucial for effective management and improved clinical outcomes. This study aimed to identify potential serum biomarkers for diagnosing PH in dogs affected with DMVD using a phosphoproteomic approach.
2023-10-30 | PXD046218 | JPOST Repository
Project description:Mitral and tricuspid valves are essential for unidirectional blood flow in the heart. They are derived from similar cell sources, and yet congenital dysplasia affecting both valves is clinically rare, suggesting the presence of differential regulatory mechanisms underlying their development. We specifically inactivated Dicer1 in the endocardium during cardiogenesis and found that Dicer1-deletion caused congenital mitral valve stenosis and regurgitation, while it had no impact on other valves. We showed that hyperplastic mitral valves were caused by abnormal condensation and extracellular matrix (ECM) remodeling. Our single-cell RNA Sequencing analysis revealed impaired maturation of mesenchymal cells and abnormal expression of ECM genes in mutant mitral valves. Furthermore, expression of a set of miRNAs that target ECM genes was significantly lower in tricuspid valves compared to mitral valves, consistent with the idea that the miRNAs are differentially required for mitral and tricuspid valve development. We thus reveal miRNA-mediated gene regulation as a novel molecular mechanism that differentially regulates mitral and tricuspid valve development, thereby enhancing our understanding of the non-association of inborn mitral and tricuspid dysplasia observed clinically.
2022-08-19 | GSE207226 | GEO