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.
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.
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.
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.
Project description:We conducted single-cell RNA sequencing analysis of mitral valve leaflets extracted from six patients, comprising three individuals with moderate-to-severe functional mitral regurgitation and three nondiseased mitral valve controls. Bioinformatics was used to identify the cell types, describe the cell functions, and investigate cellular developmental trajectories and interactions.
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.
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.
Project description:In dogs with degenerative mitral valve disease (DMVD), pulmonary hypertension (PH) is a common complication characterized by abnormally elevated pulmonary arterial pressure (PAP). Pulmonary arterial remodeling is the histopathological changes of pulmonary artery that has been recognized in PH. The underlying mechanisms that cause this arterial remodeling are poorly understood. This study aimed to perform shotgun proteomics to investigate changes in protein expression in pulmonary arteries and lung tissues of DMVD dogs with PH compared to normal control dogs and DMVD dogs without PH.
