Zusammenfassung
Emphysema is a disease of the lung parenchyma with progressive alveolar
tissue destruction that leads to peripheral airspace enlargement. In
this review, we discuss how mechanical forces can contribute to disease
progression at various length scales. Airspace enlargement requires
mechanical failure of alveolar walls. Because the lung tissue is under a
pre-existing tensile stress, called prestress, the failure of a single
wall results in a redistribution of the local prestress. During this
process, the prestress increases on neighboring alveolar walls which in
turn increases the probability that these walls also undergo mechanical
failure. There are several mechanisms that can contribute to this
increased probability: exceeding the failure threshold of the ECM,
triggering local mechanotransduction to release enzymes, altering
enzymatic reactions on ECM molecules. Next, we specifically discuss
recent findings that stretching of elastin induces an increase in the
binding off rate of elastase to elastin as well as unfolds hidden
binding sites along the fiber. We argue that these events can initiate a
positive feedback loop which generates slow avalanches of breakdown that
eventually give rise to the relentless progression of emphysema. We
propose that combining modeling at various length scales with
corresponding biological assays, imaging and mechanics data will provide
new insight into the progressive nature of emphysema. Such approaches
will have the potential to contribute to resolving many of the
outstanding issues which in turn may lead to the amelioration or perhaps
the treatment of emphysema in the future. (C) 2011 Published by Elsevier
Ltd.
Nutzer