Interbreed variation in serum serotonin (5-hydroxytryptamine) concentration in healthy dogs

Höglund, Katja; Häggström, Jens; Hanås, Sofia; Merveille, Anne-Christine; Gouni, Vassiliki; Wiberg, Maria; Willesen, Jakob L.; Entee, Kathleen Mc; Sørensen, Lars Tue; Tiret, Laurent; Seppälä, Eija H.; Lohi, Hannes; Chetboul, Valérie; Fredholm, Merete; Lequarré, Anne-Sophie; Ljungvall, Ingrid

doi:10.1016/j.jvc.2018.05.002

Cited by 18 publications

(31 citation statements)

References 48 publications

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“…Lastly, in our study, urine 5-HIAA concentrations were higher in female CKCS than male CKCS. Higher serum serotonin concentrations in female CKCS than male CKCS have also been reported in other studies (Arndt et al, 2009;Ljungvall et al, 2013;Höglund et al, 2018). Urine 5-HIAA concentrations have been regarded in behavioural studies as an indicator of stress and anxiety in dogs without evidence of heart disease.…”

Section: Discussionsupporting

confidence: 60%

“…Given the breed predisposition of MMVD in CKCS, a noteworthy finding is that CKCS have higher concentrations of circulating serotonin (i.e. in serum and platelet rich plasma) compared to many other breeds (Arndt et al, 2009;Ljungvall et al 2013;Cremer et al, 2014;Höglund et al, 2018). (Ljungvall et al, 2013;Cremer et al, 2015a).…”

Section: Accepted Manuscript Introductionmentioning

confidence: 99%

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Urine 5-hydroxyindoleacetic acid in Cavalier King Charles spaniels with preclinical myxomatous mitral valve disease

Christiansen

Cremer

Helander

et al. 2019

The Veterinary Journal

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Highlights  Urine 5-hydroxyindoleacetic acid (5-HIAA) concentrations predict progression of cardiac disease in some human conditions  Urine 5-HIAA was measured in cavalier King Charles spaniels (CKCS) with preclinical myxomatous mitral valve disease (MMVD)  Urine 5-HIAA concentrations were higher in clinic-collected samples than in morning, home-collected samples  Female CKCS showed higher urine 5-HIAA concentrations than male dogs

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Section: Discussionsupporting

confidence: 60%

Section: Accepted Manuscript Introductionmentioning

confidence: 99%

Urine 5-hydroxyindoleacetic acid in Cavalier King Charles spaniels with preclinical myxomatous mitral valve disease

Christiansen

Cremer

Helander

et al. 2019

The Veterinary Journal

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“…However, the reported CKCS predisposition to platelet dysfunction and macro-thrombocytopenia is well recognised, and macro-thrombocytopenia has been associated with early MMVD development in humans [ 7 , 10 , 12 ]. Considering these effects, and what is known about MMVD pathology, a potential role for prothrombin/thrombin in CKCS MMVD pathogenesis can be postulated, possibly through platelet interaction and enhanced 5HT signalling [ 15 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptomic profiling of myxomatous mitral valve disease in the cavalier King Charles spaniel

et al. 2020

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Background Almost all elderly dogs develop myxomatous mitral valve disease by the end of their life, but the cavalier King Charles spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is a genetic component to the condition in this breed. Transcriptional profiling can reveal the impact of genetic variation through differences in gene expression levels. The aim of this study was to determine whether expression patterns were different in mitral valves showing myxomatous degeneration from CKCS dogs compared to valves from non-CKCS dogs. Results Gene expression patterns in three groups of canine valves resulted in distinct separation of normal valves, diseased valves from CKCS and diseased valves from other breeds; the latter were more similar to the normal valves than were the valves from CKCS. Gene expression patterns in diseased valves from CKCS dogs were quite different from those in the valves from other dogs, both affected and normal. Patterns in all diseased valves (from CKCS and other breeds) were also somewhat different from normal non-diseased samples. Analysis of differentially expressed genes showed enrichment in GO terms relating to cardiac development and function and to calcium signalling canonical pathway in the genes down-regulated in the diseased valves from CKCS, compared to normal valves and to diseased valves from other breeds. F2 (prothrombin) (CKCS diseased valves compared to normal) and MEF2C pathway activation (CKCS diseased valves compared to non-CKCS diseased valves) had the strongest association with the gene changes. A large number of genes that were differentially expressed in the CKCS diseased valves compared with normal valves and diseased valves from other breeds were associated with cardiomyocytes including CASQ2, TNNI3 and RYR2. Conclusion Transcriptomic profiling identified gene expression changes in CKCS diseased valves that were not present in age and disease severity-matched non-CKCS valves. These genes are associated with cardiomyocytes, coagulation and extra-cellular matrix remodelling. Identification of genes that vary in the CKCS will allow exploration of genetic variation to understand the aetiology of the disease in this breed, and ultimately development of breeding strategies to eliminate this disease from the breed.

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“…However, the reported CKCS predisposition to platelet dysfunction and macro-thrombocytopenia is well recognised, and macro-thrombocytopenia has been associated with early MMVD development in humans [7,10,12]. Considering these effects, and what is known about MMVD pathology, a potential role for prothrombin/thrombin in CKCS MMVD pathogenesis can be postulated, possibly through platelet interaction and enhanced 5HT signalling [15,44,45].…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptomic profiling of myxomatous mitral valve disease in the Cavalier King Charles Spaniel

Markby

MacRae

Corcoran

et al. 2020

Preprint

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Background. Almost all elderly dogs develop myxomatous mitral valve disease by the end of their life, but the Cavalier King Charles Spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is a genetic component to the condition in this breed. Transcriptional profiling can reveal the impact of genetic variation through differences in gene expression levels. The aim of this study was to determine whether expression patterns were different in mitral valves showing myxomatous degeneration from CKCS dogs compared to valves from non-CKCS dogs. Results. Gene expression patterns in three groups of canine valves resulted in distinct separation of normal valves, diseased valves from CKCS and diseased valves from other breeds; the latter were more similar to the normal valves than were the valves from CKCS. Gene expression patterns in diseased valves from CKCS dogs were quite different from those in the valves from other dogs, both affected and normal. Patterns in all diseased valves (from CKCS and other breeds) were also somewhat different from normal non-diseased samples. Analysis of differentially expressed genes showed enrichment in GO terms relating to cardiac development and function and to calcium signalling canonical pathway in the genes down-regulated in the diseased valves from CKCS, compared to normal valves and to diseased valves from other breeds. F2 (prothrombin) (CKCS diseased valves compared to normal) and MEF2C pathway activation (CKCS diseased valves compared to non-CKCS diseased valves) had the strongest association with the gene changes. A large number of genes that were differentially expressed in the CKCS diseased valves compared with normal valves and diseased valves from other breeds were associated with cardiomyocytes including CASQ2, TNNI3 and RYR2. Conclusion. Transcriptomic profiling identified gene expression changes in CKCS diseased valves that were not present in age and disease severity-matched non-CKCS valves. These genes are associated with cardiomyocytes, coagulation and extra-cellular matrix remodelling. Identification of genes that vary in the CKCS will allow exploration of genetic variation to understand the aetiology of the disease in this breed, and ultimately development of breeding strategies to eliminate this disease from the breed.

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Interbreed variation in serum serotonin (5-hydroxytryptamine) concentration in healthy dogs

Abstract: Interbreed variation in serum 5-HT concentration was found in healthy dogs aged 1-7 years. These differences should be taken into account when designing clinical studies.

Cited by 18 publications

References 48 publications

Urine 5-hydroxyindoleacetic acid in Cavalier King Charles spaniels with preclinical myxomatous mitral valve disease

Urine 5-hydroxyindoleacetic acid in Cavalier King Charles spaniels with preclinical myxomatous mitral valve disease

Comparative transcriptomic profiling of myxomatous mitral valve disease in the cavalier King Charles spaniel

Comparative transcriptomic profiling of myxomatous mitral valve disease in the Cavalier King Charles Spaniel

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