Genomic expression patterns of mitral valve tissues from dogs with degenerative mitral valve disease
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ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE11460 | GEO | 2008/05/15
SECONDARY ACCESSION(S): PRJNA106375
REPOSITORIES: GEO
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Project description:Evaluation of global expression patterns provides a molecular portrait of mitral valve disease, yields insight into the pathophysiologic aspects of DMVD, and identifies intriguing genes and pathways for further study. (Am J Vet Res 2006;67:1307–1318) Keywords: control vs diseased 4 controls( beagle crosses) and 4 affected (1 Daschund, 1 Lhasa apso, 2 miniature poodles)
2008-05-15 | E-GEOD-11460 | biostudies-arrayexpress
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:In this study, we carried out a large-scale proteome profiling of human mitral valve tissues resected from patients with mitral valve prolapse.
2015-05-07 | PXD000774 | Pride
Project description:Mitral valve interstitial Tissue: Myxomatous P2 prolapse of the mitral valve vs. Control
| PRJNA431911 | ENA
Project description:BackgroundSeveral risk factors already have been determined for dogs with degenerative mitral valve disease (DMVD). Risk factors often have been considered in isolation and have not always taken into account additional information provided by the history and physical examination (PE).Hypothesis/objectivesData obtained from history and PE of dogs with DMVD provide prognostic information and can be used for risk stratification.AnimalsClient-owned dogs (n = 244) with DMVD recruited from first opinion practice.MethodsProspective longitudinal follow-up of dogs with DMVD. History and PE data were obtained at 6-month intervals and analyzed with time-dependent Cox models to derive relative risk of cardiac death. Independent hazard ratios were used to derive a clinical severity score (CSS), the prognostic value of which was evaluated by analyzing the median survival times for different risk groups and ROC analysis. Analysis of the progression of CSS over time also was undertaken.ResultsHistory of cough, exercise intolerance, decreased appetite, breathlessness (difficulty breathing) and syncope with PE findings of heart murmur intensity louder than III/VI and absence of respiratory sinus arrhythmia were independently associated with outcome and allowed development of the CSS. Clinical severity score distinguished groups of dogs with significantly different outcomes.Conclusions and clinical importanceRoutinely obtained clinical findings allow risk stratification of dogs with DMVD. Results of ancillary diagnostic tests may be complementary to history and PE findings and always should be interpreted in conjunction with these findings.
| S-EPMC4895509 | biostudies-literature
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:BackgroundDescribing severity of mitral regurgitation (MR) in dogs with degenerative mitral valve disease (DMVD) is challenging.Hypothesis/objectivesMitral regurgitant fraction (RF), effective regurgitant orifice area (EROA), and the ratio of mitral regurgitant to aortic flow (QMR :QAo ) can be calculated from routine echocardiographic measurements and provide additional information regarding MR severity.AnimalsFifty-seven dogs with preclinical DMVD including 36 without and 21 with cardiomegaly.MethodsProspective observational study. The expected relationships among RF, EROA, and QMR :QAo and 1-dimensional measurements including left atrium to aortic root diameter ratio (LA:Ao) and normalized left ventricular internal dimension at end-diastole (LVIDdN) were mathematically derived and calculated using echocardiographic data from the study population. Nonlinear goodness of fit was determined by calculation of the root mean standard error. The correlations between 1-dimensional and multidimensional indices were analyzed using receiver operating characteristic curves.ResultsThe relationships among RF, EROA, QMR :QAo , and both LA:Ao and LVIDdN were curvilinear, and the multidimensional indices differentiated MR of variable severity. By contrast, 1-dimensional measurements were insensitive to MR severity until RF equaled or exceeded 50%. Regurgitant fraction ≥50%, EROA to body surface area ≥0.347 and QMR :QAo ≥0.79 were strongly associated with LA:Ao ≥1.6 and LVIDdN ≥1.7.Conclusions and clinical importanceRegurgitant fraction, EROA, and QMR :QAo quantify MR severity in dogs with preclinical DMVD in a manner that 1-dimensional measurements do not.
| S-EPMC6430891 | biostudies-literature
Project description:Genome-wide association study (GWAS) is a powerful tool for identifying the genetic causes of various diseases. This study was conducted to identify genomic variation in Maltese dog genomes associated with degenerative mitral valve disease (DMVD) development and to evaluate the association of each biological condition with DMVD in Maltese dogs. DNA was extracted from blood samples obtained from 48 Maltese dogs (32 with DMVD and 16 controls). Genome-wide single nucleotide polymorphism (SNP) genotyping was performed. The top 30 SNPs from each association of various conditions and genetic variations were mapped to their gene locations. A total of 173,662 loci were successfully genotyped, with an overall genotype completion rate of 99.41%. Quality control analysis excluded 46,610 of these SNPs. Manhattan plots were produced using allelic tests with various candidate clinical conditions. A significant peak of association was observed between mitral valve prolapse (MVP) and SNPs on chromosome 17. The present study revealed significant SNPs in several genes associated with cardiac function, including PDZ2, Armadillo repeat protein detected in velo-cardio-facial syndrome, catenin (cadherin-associated protein) alpha 3, low-density lipoprotein receptor class A domain containing protein 4, and sterile alpha motif domain containing protein 3. To our knowledge, this is the first study of a genetic predisposition to DMVD in Maltese dogs. Although only a limited number of cases were analyzed, these data could be the basis for further research on the genetic predisposition to MVP and DMVD in Maltese dogs.
| S-EPMC6351756 | biostudies-literature
Project description:Rational: We previously reported evidence of endothelial to mesenchymal transition (EndMT) and fibrosis in mitral valve (MV) leaflets at two to six months post-myocardial infarction (MI) in sheep. The onset of these changes and the mechanism of their instigation are not known. Early modulation of EndMT and fibrosis in MV leaflets may limit the development of ischemic mitral regurgitation (IMR) and heart failure. H Objective: To test the hypothesis that circulating molecules present in plasma within days after MI incite EndMT and fibrotic processes in MV leaflets. Method and Results: Ovine MVs harvested 8-10 days after inferior MI (IMI) showed an increase in MV thickness by histology and onset of EndMT, shown by increased CD31/α-smooth muscle actin (α-SMA)+ cells in post-MI MV leaflets (10.5±6.9%) versus sham (2.6±4%). In vitro, post-MI plasma induced EndMT and pro-fibrotic markers and enhanced migration of primary mitral valve endothelial cells (VECs). In contrast, sham plasma did not, despite the presence of TGFβ2 at levels known to induce EndMT in VECs (2 ng/ml). Analysis of sham versus post-MI plasma using a cytokine array revealed a significant drop in the Wnt signaling antagonist secreted frizzled-related protein 3 (sFRP3) in post-MI plasma compared to sham plasma, which was confirmed by ELISA. Addition of recombinant sFRP3 to post-MI plasma reversed its EndMT-inducing effect on mitral VECs, measured by restored VE-cadherin, reduced α-SMA, and reduced TGFβ1-3 expression. Extracellular signal related kinase 1/2 and SMAD2/3 phosphorylation were increased in mitral VEC by post-MI plasma, and both were blocked by supplementing the post-MI plasma with sFRP3. RNA-seq analysis of mitral VECs exposed to post-MI versus sham plasma for 24 hours showed upregulated forkhead box M1 (FOXM1), a transcription factor previously shown to drive fibrosis. FOXM1 was co-localized with CD31 in MV leaflets obtained from sheep at 8-10 days post-MI, which suggests FOXM1 may be linked to EndMT initiation. Blocking FOXM1 with Siomycin A (Sio A) reduced EndMT and pro-fibrotic transcripts in post-MI plasma treated mitral VECs. Finally, post-MI plasma-induced and TGFβ-induced FOXM1 was downregulated by sFRP3. Conclusions: Reduced sFRP3 in post-MI plasma appears to facilitate the onset of TGFβ-driven EndMT and fibrosis in mitral VECs by increasing the transcription factor FOXM1. Restoring sFRP3 levels and/or inhibiting FOXM1 may provide new strategies to minimize maladaptive changes that occur in the MV due to MI.
2022-01-15 | GSE182696 | GEO
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