First 10 Month Report; 15th November 2004.
Mitral Valve Disease Project
Investigators; Dr Brendan Corcoran & Mr Richard
Hospital for Small Animals
Easter Bush Veterinary Centre
University of Edinburgh
The aim of this study is to characterise the cellular changes that occur in the
mitral valve of dogs with myxomatous degeneration. The hypothesis is that altered
cell function changes the way in which the structural components of the valve
(mainly collagen) are produced, broken down in the valve, are organised and metabolised,
and so affect the structural integrity of the valve resulting in a murmur.
The initial period of any PhD research involves the PhD student identifying what
information is already available in the published literature (both human and veterinary)
and identifying potential research of promise. The student should also consolidate
any work in hand or close to completion and explore possible novel avenues for
2.1. Tissue Collection
So far the project has developed a system for tissue collection and has obtained
promise of assistance from the main Cardiology Referral practices in the UK, has
developed potential collaborative links with researchers in Scandinavia and the
USA and has identified a potentially valuable sources of valve material from colleagues
in Sweden. Valve material has been collected from 20 affected dogs and has been
processed for a variety of purpose.
2.2. Cell Characterisation Studies
Affected valves have been assessed for the presence of a variety of markers that
allow us to identify cell types. These markers included vimentin, desmin, smooth
muscle actin and myosin. Additionally, work has begun in determining if there
is increased cell enzymatic activity (which could result in valve destruction)
and data is now available for the expression of an enzyme known as MMP-2.
2.3. Ultrastructural Morphology
We are also interested in reviewing the pathology of mitral valve disease and
have been evaluating the structural changes to the valve using routine and special
stains for light microscopy. This allows us to describe in greater detail than
previous what changes are occurring in the valve. In association with this work
we are investigating changes in cell numbers in disease valve areas, and had a
vacation scholarship student (funded by the Veterinary School) for 8 weeks in
the summer to assist with this part of the project.
2.4. Protein Expression
Some preliminary work has been carried out looking at the expression of immunoglobulins
in affected dogs and has provided interesting, although puzzling initial findings.
This work is using a technique known as Western Blotting and further work will
be carried out in due course.
3. Further Developments
In order to explore new avenue of research and formulate new ideas as to what
way be happening in disease valves, we have been in discussion with molecular
geneticists on applying some new techniques. To that end we are actively seeking
additional financial support to cover the consumable costs of such work.
We have recently appointed an additional self-funding PhD study to supplement
the current work, and now have collaborative involvement with a colleague biochemist,
which has given us access to state-of-the art tissue imaging facilities in Darnesbury
(near Warrington) and Trieste in Northern Italy. These techniques will allow us
to look more closely at structural elements (collagen and elastin) in the valves
and determine the nature of the structural alteration that is present in diseased
animals. This is a totally novel use of this technique in Valve research either
in human and animals.
4. Communications and Publications
We have presented work to date at a prestigious international conference on mitral
valve disease in Paris (29th - 31st October 2004). We have submitted an abstract
for presentation at the British Small Animal Veterinary Association meeting in
April 2005. And details of the work will also be presented at the Veterinary Cardiovascular
Society Winter meeting in Longhborough.
A second paper describing the changes in cell type seen with mitral valve disease
has just been accepted for publication in the American Journal of Veterinary Research
(the most widely read veterinary research journal in the world).
All these presentations and published articles have fully acknowledged the contribution
of the CKCS Club and the Kennel Club and serve to heighten awareness of this disease
and the effects that are being made to find out the cause of mitral valve disease.
5. Future Plans
The future plan is to consolidate the work done so far. This mainly involves completion
of work using as many tissue samples as possible. In tandem with this will be
the exploration of new avenue of research so we can get as complete a picture
as possible of what is happening in diseased valves.
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Material Copyright © 2005 The Cavalier King Charles Spaniel Club