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|Title: ||Morphological, cellular and proteomic features of canine myxomatous mitral valve disease|
|Authors: ||Han, Richard I-Ming|
|Supervisor(s): ||Corcoran, Brendan M.|
Pemberton, Alan D.
|Issue Date: ||2009|
|Publisher: ||The University of Edinburgh|
|Abstract: ||Myxomatous mitral valve degeneration (MMVD) is the single most common
cardiac disease of the dog, and is analogous to Mitral Valve Prolapse in humans.
Very little is known about the aetiopathogenesis of this disease or the changes in
valvular interstitial cell populations in diseased valves. The aim of this study was to
identify morphological, cellular and molecular changes associated with MMVD.
Mitral valve leaflets from both normal and varying grades (Whitney’s 1-4) of
diseased dogs were subject to image analysis, immunophenotyping, proteomics and
Image analysis - leaflet thickening due to accumulation of
glycosaminoglycan was significant in this disease. MMVD is associated with loss of
connective tissue, reduction in cell numbers but no change in cell shape in the
overtly myxomatous area. Near the surface, increase in valvular interstitial cells
(VIC) towards the damaged endothelium in concert with destruction of collagen and
building up of ground substance was manifested during the disease process.
Immunophenotyping - activated myofibroblasts were increased and
fibroblast-like VICs were reduced without any change in desmin and myosin
expression in MMVD compared to clinical normal dogs. In addition, other cell types
like macrophage, adipocyte, chondrocyte, mast cell, and stem cell were identified
and their possible role in MMVD is discussed.
Proteomics - a protein expression profile was established, with 64 proteins
being positively identified from dog’s mitral valve using 1-D SDS PAGE LC/MS.
Amongst them 44 proteins were differentially expressed comparing normal and
severely diseased. Two actin binding proteins, tropomyosin alpha and myosin light
chain-2 were found to be differentially expressed in the normal but down regulated
in the diseased.
RT-PCR was used to assess the expression of 8 genes of interest. Their
expression was compared with 3 different housekeeping genes.|
|Sponsor(s): ||Kennel Club|
Cavalier King Charles Club
|Keywords: ||Myxomatous mitral valve degeneration|
|Appears in Collections:||Royal (Dick) School of Veterinary Studies thesis and dissertation collection|
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