Mitral valve transcriptome analysis in thirty-four age-matched Cavalier King Charles Spaniels with or without congestive heart failure caused by myxomatous mitral valve disease

Abstract

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.

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

“…Such information unveils relevant signaling pathways that can then be investigated in greater detail and functionally assessed, offering powerful insights into gene functions in the disease [11]. Additionally, abundant transcriptome data reported in several studies in dogs with MMVD [12,13] may reveal consistent changes, facilitating hypothesis-driven studies examining putative signaling pathways involved in disease pathogenesis and identifying active genes in MMVD. Therefore, further research at the transcriptomic level is necessary to achieve a more precise diagnosis and understand the intricate molecular mechanisms underlying MMVD stages.…”

Pulmonary Hypertension Secondary to Myxomatous Mitral Valve Disease in Dogs: Current Insights into the Histological Manifestation and Its Determining Factors

“…The most common cause of mitral valve regurgitation is myxomatous mitral valve degeneration (MMVD) [1,2]. Analysis of the population of dogs with MMVD indicates that the development of the disease has a genetic basis, and it is particularly conserved in the population of Cavalier King Charles Spaniels [3][4][5][6]. The disease leads to non-inflammatory degenerative changes in the mitral valve leaflet margins, resulting in thickening.…”