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Title: Investigations into the development of chronic degenerative valve disease in dogs
Author: Vloumidi, Eleni I.
ISNI:       0000 0004 2742 5690
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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In dogs chronic degenerative valve disease (CDVD) is the most common cardiac disorder and the most frequent cause of cardiac failure seen in clinical practice. The aetiology of CDVD is unknown however recent investigations have focused on the molecular mechanisms that may be implicated in the development of the disease. This thesis investigates the impact of mechanical stimuli on the canine mitral valve at both the molecular and clinical level. At the molecular level canine valvular interstitial cells (VICs) were successfully extracted from valve tissue and shown to express proteins related to both the contractile and synthetic properties of the valve; therefore they were characterized as myofibroblasts. Furthermore, no change in phenotype after freezing and thawing was evident suggesting that freezing had no effect on the integrity and the contractile, synthetic and metabolic properties of the cells. This was demonstrated by maintenance of the expression of alpha-smooth muscle actin (ASMA), prolyl-4-hydroxylase (4-HP) and creatine kinase B (CK-B) respectively. Mitral VICs (MVICs) had greater contractile and synthetic properties than tricuspid VICs (TVICs), evidenced by a higher expression of ASMA and 4-HP. This difference was likely to be a consequence of exposure to higher pressures throughout the cardiac cycle. It was also demonstrated that canine MVICs from both normal and diseased valves respond to mechanical stretch by hypertrophy, increasing the production of protein per unit cell. Furthermore, MVICs of both normal and diseased valves lose their contractile phenotype in response to mechanical stretch, indicated by a fall in ASMA expression. It was also demonstrated that the MVICs of diseased German shepherd dogs were more resistant to stretch than the MVICs of normal and diseased beagles. At the clinical level no gross lesions were observed echocardiographically on the mitral valves of the greyhounds irrespective of the dogs' age and training status. This suggests that the mitral valves of the greyhounds are more resistant to mechanical stimuli. However, these dogs develop mitral regurgitation with advancing age possibly due to alterations in heart geometry.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available