RNA sequencing provides novel insights into the pathogenesis of naturally occurring myxomatous mitral valve disease stage B1 in beagle dogs.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Dog Diseases*/genetics ; Dog Diseases*/pathology ; Sequence Analysis, RNA*; Animals ; Dogs ; Male ; Female ; Mitral Valve/pathology ; Heart Valve Diseases/genetics ; Heart Valve Diseases/veterinary ; Heart Valve Diseases/pathology ; Transcriptome ; Prospective Studies ; Gene Expression Profiling

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing.
Competing Interests: The authors have declared no conflicts of interest in relation to the research, authorship or publication of this article
(Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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Date Created: 20240516 Date Completed: 20240516 Latest Revision: 20240518

20240518

PMC11098313

10.1371/journal.pone.0300813

38753730