Cardiomics in canine acquired heart diseases: Histopathological, proteomic, and transcriptomic analyses

Sorawit Phetariyawong

doi:10.54612/a.6o80hbgfgd

Cardiomics in canine acquired heart diseases: Histopathological, proteomic, and transcriptomic analyses

Bidragets översatta titel: Kardiomik vid förvärvade hjärtsjukdomar hos hundar: histopatologiska, proteomiska och transkriptomiska analyser

Sorawit Phetariyawong

Institutionen för kliniska vetenskaper

Publikation: Avhandling › Doktorsavhandling

6 Nedladdningar

Sammanfattning

Myxomatös mitralisklaffsjukdom (MMVD) och dilaterad kardiomyopati (DCM) är
två av de vanligaste hjärtsjukdomarna hos hund. Mekanismerna bakom MMVD och
DCM är fortfarande ofullständigt kartlagda. Den här avhandlingen syftade till att
systematiskt undersöka och jämföra patologiska och molekylära förändringar
associerade med MMVD och DCM hos hundar genom analys av hjärtvävnad med
kompletterande histopatologiska, proteomiska och transkriptomiska metoder.
Avhandlingen inkluderade hundar med MMVD (n = 42), DCM (n = 16) och
hjärtfriska kontroller (n = 32). Histopatologiska fynd utvärderades i flera,
regionmatchade hjärtprover med kvantitativa och kvalitativa histopatologiska
metoder. Prover från vänsterkammares (LV) laterala vägg och bakre papillärmuskel
(PPM) analyserades med proteomiska metoder, medan PPM-prover från 24 Cavalier
King Charles spaniels analyserades med transkriptomiska metoder.
Hundar med MMVD hade mer fibros och fettinfiltration, främst i hjärtats vänstra
regioner, medan hundar med DCM hade en högre grad av förmaksfibros än
kontroller, med mer omfattande fibros hos hundar med förmaksflimmer (AF) än hos
hundar utan AF. Varken graden av artärförträngning eller förekomsten av tunna,
vågiga hjärtmuskelfibrer skilde sig mellan grupperna i någon del av hjärtat. Hos
hundar med MMVD var förändringar i proteinuttryck i LV främst associerade med
metabolism av fettsyror och grenade aminosyror, medan motsvarande förändringar
hos de med DCM främst var associerade med muskelcellshomeostas och
glukosmetabolism. Genuttrycksförändringar hos hundar med MMVD och
vänstersidig hjärtförstoring var associerade med cytoskelettets struktur.
Sammanfattningsvis omfattade de histopatologiska förändringarna hos hundar
med MMVD främst vänster sida av hjärtat, medan de hos hundar med DCM
omfattade båda sidor av hjärtat. Proteomisk analys indikerade skilda metaboliska
processer associerade med två sjukdomarna, medan transkriptomisk analys
indikerade att strukturell ombyggnad av LV PPM kan bidra till patofysiologin vid
MMVD.

Bidragets översatta titel	Kardiomik vid förvärvade hjärtsjukdomar hos hundar: histopatologiska, proteomiska och transkriptomiska analyser
Originalspråk	Engelska
Kvalifikation	Doktor i filosofi
Förlag	Swedish University of Agricultual Sciences
Tryckta ISBN	978-91-8124-358-1
Elektroniska ISBN	978-91-8124-408-3
DOI	https://doi.org/10.54612/a.6o80hbgfgd
Status	Publicerad - 2026

Nyckelord

klaffsjukdom
hjärtmuskelsjukdom
patologi
molekylärbiologi

SLU-serie

Acta Universitatis Agriculturae Sueciae

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10.54612/a.6o80hbgfgd

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@phdthesis{6dd9afda564b4a27992f2a594c1f6ec3,

title = "Cardiomics in canine acquired heart diseases: Histopathological, proteomic, and transcriptomic analyses",

abstract = "Myxomatous mitral valve disease (MMVD) and dilated cardiomyopathy (DCM) are two of the most common cardiac diseases in dogs. The mechanisms underlying MMVD and DCM remain incompletely understood. This thesis aimed to systematically explore and compare pathological and molecular changes associated with MMVD and DCM in dogs by evaluating cardiac tissue using complementary histopathological, proteomic, and transcriptomic approaches. Dogs with MMVD (n = 42), DCM (n = 16), and cardiac-healthy controls (n = 32) were enrolled in this thesis. Histopathological features were evaluated in multiple, region-matched cardiac tissue samples using quantitative and qualitative histopathological methods. Samples from the left ventricular (LV) lateral wall and posterior papillary muscle (PPM) were analyzed using proteomics, whereas PPM samples from 24 Cavalier King Charles Spaniels were analyzed using transcriptomics. Dogs with MMVD had a higher degree of fibrosis and fatty infiltration, predominantly in left-sided cardiac regions, than controls. Dogs with DCM had a higher degree of atrial fibrosis than controls, with more extensive fibrosis in dogs with atrial fibrillation (AF) than in those without AF. Neither arterial lumen-to-area ratio nor the presence of attenuated wavy fibers differed among the groups in any cardiac region. The LV protein expression profiles of dogs with MMVD reflected a shift in energy metabolism towards increased reliance on fatty acid and branchedchain amino acid, whereas those of dogs with DCM primarily reflected alterations in muscle cell homeostasis and glucose metabolism. Gene expression changes in dogs with MMVD-associated left-sided cardiac enlargement primarily involved polymeric cytoskeletal fiber components. In conclusion, histopathological changes in dogs with MMVD predominantly involved the left-sided heart, whereas in dogs with DCM, they involved both sides of the heart. Proteomic analysis suggested distinct metabolic processes associated with the two diseases, while transcriptomic analysis indicated that structural remodeling of the LV PPM may contribute to the pathophysiology of MMVD. ",

keywords = "valvular heart disease, myocardial disease, pathology, molecular biology, klaffsjukdom, hj{\"a}rtmuskelsjukdom, patologi, molekyl{\"a}rbiologi",

author = "Sorawit Phetariyawong",

year = "2026",

doi = "10.54612/a.6o80hbgfgd",

language = "English",

isbn = "978-91-8124-358-1",

series = "Acta Universitatis Agriculturae Sueciae",

publisher = "Swedish University of Agricultual Sciences",

number = "2026:61",

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TY - BOOK

T1 - Cardiomics in canine acquired heart diseases

T2 - Histopathological, proteomic, and transcriptomic analyses

AU - Phetariyawong, Sorawit

PY - 2026

Y1 - 2026

N2 - Myxomatous mitral valve disease (MMVD) and dilated cardiomyopathy (DCM) are two of the most common cardiac diseases in dogs. The mechanisms underlying MMVD and DCM remain incompletely understood. This thesis aimed to systematically explore and compare pathological and molecular changes associated with MMVD and DCM in dogs by evaluating cardiac tissue using complementary histopathological, proteomic, and transcriptomic approaches. Dogs with MMVD (n = 42), DCM (n = 16), and cardiac-healthy controls (n = 32) were enrolled in this thesis. Histopathological features were evaluated in multiple, region-matched cardiac tissue samples using quantitative and qualitative histopathological methods. Samples from the left ventricular (LV) lateral wall and posterior papillary muscle (PPM) were analyzed using proteomics, whereas PPM samples from 24 Cavalier King Charles Spaniels were analyzed using transcriptomics. Dogs with MMVD had a higher degree of fibrosis and fatty infiltration, predominantly in left-sided cardiac regions, than controls. Dogs with DCM had a higher degree of atrial fibrosis than controls, with more extensive fibrosis in dogs with atrial fibrillation (AF) than in those without AF. Neither arterial lumen-to-area ratio nor the presence of attenuated wavy fibers differed among the groups in any cardiac region. The LV protein expression profiles of dogs with MMVD reflected a shift in energy metabolism towards increased reliance on fatty acid and branchedchain amino acid, whereas those of dogs with DCM primarily reflected alterations in muscle cell homeostasis and glucose metabolism. Gene expression changes in dogs with MMVD-associated left-sided cardiac enlargement primarily involved polymeric cytoskeletal fiber components. In conclusion, histopathological changes in dogs with MMVD predominantly involved the left-sided heart, whereas in dogs with DCM, they involved both sides of the heart. Proteomic analysis suggested distinct metabolic processes associated with the two diseases, while transcriptomic analysis indicated that structural remodeling of the LV PPM may contribute to the pathophysiology of MMVD.

AB - Myxomatous mitral valve disease (MMVD) and dilated cardiomyopathy (DCM) are two of the most common cardiac diseases in dogs. The mechanisms underlying MMVD and DCM remain incompletely understood. This thesis aimed to systematically explore and compare pathological and molecular changes associated with MMVD and DCM in dogs by evaluating cardiac tissue using complementary histopathological, proteomic, and transcriptomic approaches. Dogs with MMVD (n = 42), DCM (n = 16), and cardiac-healthy controls (n = 32) were enrolled in this thesis. Histopathological features were evaluated in multiple, region-matched cardiac tissue samples using quantitative and qualitative histopathological methods. Samples from the left ventricular (LV) lateral wall and posterior papillary muscle (PPM) were analyzed using proteomics, whereas PPM samples from 24 Cavalier King Charles Spaniels were analyzed using transcriptomics. Dogs with MMVD had a higher degree of fibrosis and fatty infiltration, predominantly in left-sided cardiac regions, than controls. Dogs with DCM had a higher degree of atrial fibrosis than controls, with more extensive fibrosis in dogs with atrial fibrillation (AF) than in those without AF. Neither arterial lumen-to-area ratio nor the presence of attenuated wavy fibers differed among the groups in any cardiac region. The LV protein expression profiles of dogs with MMVD reflected a shift in energy metabolism towards increased reliance on fatty acid and branchedchain amino acid, whereas those of dogs with DCM primarily reflected alterations in muscle cell homeostasis and glucose metabolism. Gene expression changes in dogs with MMVD-associated left-sided cardiac enlargement primarily involved polymeric cytoskeletal fiber components. In conclusion, histopathological changes in dogs with MMVD predominantly involved the left-sided heart, whereas in dogs with DCM, they involved both sides of the heart. Proteomic analysis suggested distinct metabolic processes associated with the two diseases, while transcriptomic analysis indicated that structural remodeling of the LV PPM may contribute to the pathophysiology of MMVD.

KW - valvular heart disease

KW - myocardial disease

KW - pathology

KW - molecular biology

KW - klaffsjukdom

KW - hjärtmuskelsjukdom

KW - patologi

KW - molekylärbiologi

UR - https://res.slu.se/id/publ/6dd9afda-564b-4a27-992f-2a594c1f6ec3

U2 - 10.54612/a.6o80hbgfgd

DO - 10.54612/a.6o80hbgfgd

M3 - Doctoral thesis

SN - 978-91-8124-358-1

T3 - Acta Universitatis Agriculturae Sueciae

PB - Swedish University of Agricultual Sciences

ER -