4 MATERIAL AND METHODS
6.6 Implications for further studies
1. The analysis of IL-1, IL-2, MMP-1, -3, and TIMP-3 mRNA and protein (these were increased in the blood and myocardium of diseased dogs) in blood samples of dogs in different stages of cardiac diseases and its correlation with echocardiographic investigations that assess myocardial morphology and function would detect changes in progression of disease and identify potential biomarkers for cardiac remodelling.
2. Further characterisation of myocardial remodelling by investigating the protein expression of inflammatory and ECM remodelling markers, the presence of fibrosis, myocardial degeneration and apoptosis, activation of endothelial cells, infiltration of inflammatory cells and the presence of cardiac stem cells would reveal further details of the pathogenesis of cardiac diseases.
3. Increasing the sample size of one cardiac disease, i.e. DCM, and the correlation of clinical findings and echocardiographic results with parameters of cardiac
inflammation and remodelling would strengthen the significance of the results and possibly identify clinical parameters of cardiac inflammation and remodelling.
4. The correlation of echocardiographic results with the expression of inflammatory and ECM remodelling markers in the blood and, if available, the myocardium of dogs with systemic diseases and the association of these results with survival of these dogs would allow further assessment of the importance and the time course of cardiac impairment and remodelling in dogs with systemic diseases.
5. Further investigation of the role of leptin in cardiac cachexia and in obese dogs and its association with cardiac function are of interest and would reveal the real significance of leptin in canine cardiac diseases. Furthermore, the investigation of other adipocytokines, such as adiponectin, resistin, visfatin, which were reported to be involved in human cardiac diseases, would give information on their role in canine cardiac diseases.
7 CONCLUSIONS
I Studies investigating the role of inflammation and ECM remodelling in dogs with cardiac and systemic diseases in comparison to healthy controls (Studies I, II and III) led to the following conclusions.
1. The significantly higher expression of all markers of inflammation and ECM remodelling in the myocardium of dogs with cardiac diseases in comparison to hearts of healthy control dogs, whilst only single markers were elevated in the blood of dogs with cardiac diseases, suggest primary myocardial inflammation and ECM remodelling in dogs with cardiac diseases and not a myocardial response to circulating inflammatory mediators.
2. The higher transcription levels of most markers of inflammation and ECM remodelling in atria than ventricles of dogs cardiac and systemic diseases, which matched with the observed extent of pathological changes in dogs with cardiac diseases, suggest different remodelling processes depending on localisation.
These differences in inflammation and ECM remodelling are likely to contribute to progression of disease, cardiac dysfunction and development of arrhythmias.
3. The increased expression of inflammatory and ECM remodelling markers in the myocardium of dogs with systemic diseases not involving the heart, in the absence of histological changes in the heart, might indicate acute functional changes in end-stage diseases. The apparent inflammatory state of the myocardium of dogs with systemic diseases might be acute and reversible or might contribute to morbidity and mortality of these dogs.
4. The constitutive expression of profibrotic markers in the myocardium of healthy control dogs suggests a regenerative and profibrotic potential of the healthy canine myocardium.
II The increased transcription of leptin in the blood and myocardium of dogs with cardiac diseases (Study IV) and the simultaneous elevation of inflammatory and ECM remodelling markers (Studies II and III) suggest an involvement of leptin in cardiac inflammation and remodelling in dogs with cardiac diseases.
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