Michael wrote:

> why one tissue forms one type of fiber/bundle
> structure while another forms a different kind.
> For the aortic valve, at least, there have been
> computational models done by Charles Peskin that
> suggest that mechanical equilibrium is best
> satisfied with the formation of dense cords, which
> are clearly observable by the eye. Thus,
> macro-stress fields may be one reason for
> particular meso-structural connective tissue
> formations in tissues.
This has been the currently accepted mechanism for many years, but
recently, I've been less and less convinced that it works, based on
my experience with studying the microstructure of the aortic valve.

The aortic valve is a really weird piece of connective tissue, in
the sense that is does not readily remodel in response to stress.
I've looked at literally hundreds of explanted diseased aortic
valves, and their gross morphology suggest that they are all the
same. When they are diseased, they are horribly calcified, and when
they are healthy, they have very similar gross structure. Although
I have not specifically correlated collagen content with patient
activity (and hence the applied stress), there does not appear to be
much variability in gross terms. Moreover, very large leaflets,
from patients with dilated aortas, do not have thickened leaflets,
as the adaptation to larger loads would suggest. There is also some
anecdotal evidence (and if someone has a good reference I'd sure
like to see it) that heart valve collagen is very highly
crosslinked, implying that it is very old. All this points to my
supposition that the aortic valve does not remodel in the
traditional sense.

Moreover, lets look at what happens during embryogenesis and fetal
development. When the heart starts to beat in the fetus, the aortic
valve tissue is already very well differentiated. This means that
the highly complex structure of fiber layers, fiber bundles
coalescing together at the commissures, all that complexity has
arisen in the ABSENCE of any dynamic stresses. I think that
collagen organization, at least in the aortic valve, is
preprogrammed into the cells that fabricate it. Unfortunately for
us, these cells are long gone by the time we get the tissues.....

Ivan Vesely, Ph.D.
Associate Staff
Department of Biomedical Engineering
Cleveland Clinic Foundation

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