The immunohistochemical evaluation of selected markers in the left atrium of dogs with end-stage dilated cardiomyopathy and myxomatous mitral valve disease – a preliminary study

Abstract

BackgroundDilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD) are the most common diseases noted in dogs. Although their pathogenesis varies, both include a significant enlargement of the left atrium.The study was carried out on left atrial specimens obtained from 56 dogs, including those from 34 dogs with clinically diagnosed MMVD, 15 dogs with DCM and 7 dogs without heart disease (control group). Dogs in the MMVD and the DCM groups presented with left atrial enlargement and stage D heart failure. The specimens underwent immunohistochemical examination using desmin, vimentin, periostin and caspase-3 antibodies.ResultsThere were alterations in the expression of the studied proteins in the study groups compared to the control group. The changes included: irregularity of desmin cross-striation and desmosomes, a higher amount of vimentin-positive cells, a change in the periostin expression pattern from cytoplasmic to extracellular, and a lower expression of caspase-3. The alterations were more pronounced in the DCM group than in the MMVD group.ConclusionsDuring heart failure, the pattern of desmin, vimentin, periostin and caspase-3 expression alters in the left atrium, regardless of the cause. The changes are more pronounced in dogs with DCM than in dogs with MMVD and similar left atrial enlargement, suggesting that volume overload may not be the only cause of myocardial changes in DCM.

Cardiomyocyte marker expression in dogs with left atrial enlargement due to dilated cardiomyopathy or myxomatous mitral valve disease

“…Forty dogs underwent a standard clinical and cardiological examination with ECG, an echocardiographic examination and 24-hour ECG (Holter) monitoring in cases where rhythm disturbances were suspected as described in our previous study [11]. After the examination, dogs in the DCM and the MMVD group underwent appropriate treatment to reduce the effects of progressive heart failure and/or arrhythmias, and were checked every 6 months or more frequently if necessary www.fhc.viamedica.pl until the moment of death or euthanasia.…”

“…Each specimen was randomly assigned a number to allow a blinded examination. The specimens were stained with hematoxylin-eosin or Masson-Goldner trichrome methods and evaluated for interstitial and perivascular fibrosis, cardiomyocyte degeneration (including cardiomyocyte nuclei enlargement, loss of cross striation and altered cardiomyocyte structure), intramyocardial arterial narrowing and inflammatory infiltrates as described in our previous studies [11,12]. Each of the features was evaluated in 20 randomly chosen fields per slide (for interstitial fibrosis, cardiomyocyte degeneration and inflammatory infiltrates) or in at least 10 vessels per slide (for perivascular fibrosis and intramyocardial arterial narrowing).…”

“…Each of the features was evaluated in 20 randomly chosen fields per slide (for interstitial fibrosis, cardiomyocyte degeneration and inflammatory infiltrates) or in at least 10 vessels per slide (for perivascular fibrosis and intramyocardial arterial narrowing). An average score was counted for each feature in every specimen as described previously [11,12].…”

“…Our previous study [11] showed that in dogs with congestive heart failure and left atrial enlargement various myocardial proteins undergo changes in their expression in left atrial myocardium. Based on that preliminary study we decided to further explore the alterations in the left atrial cardiomyocytes during heart failure due to DCM and MMVD, including the expression of sarcoplasmic reticulum Ca 2+ ATPase 2A-1 (SERCA1) protein, sarcoplasmic reticulum Ca 2+ ATPase 2A-2 (SERCA2) protein, sarcomeric alpha--actinin (SA), alpha-smooth muscle actin (SMA), and dystrophin (DMD).…”

“…During heart failure various myocardial proteins (including proteins of cardiomyocyte and extracellular matrix) present altered expression in heart muscle [8][9][10][11]. Atrial tissue undergoes different remodeling, as compared to ventricular cardiac muscle in various heart diseases, including DCM and congestive heart failure associated with arrhythmia [6,12,13].…”