Biology Reference
In-Depth Information
result, most diseases characterized by elastolysis such as emphysema, aortic aneu-
rysm, and “aging skin” take decades to manifest.
Unfortunately, as difficult as it is to degrade elastin, it also appears that elastin has
a very limited capacity for repair. Elastic fiber assembly requires the coordinated
secretion of tropoelastin onto a microfibrillar scaffold accompanied by cross-linking
of elastin by lysyl oxidases. Adult vertebrates appear to have limited capacity to
temporally and spatially coordinate this complex process following growth and
development.
Interestingly, as a group, the elastases appear to have a variety of interesting and
unique functions beyond their capacity to degrade matrix components. Moreover,
elastin fragments themselves have a variety of important biological functions. This
chapter will discuss both the importance of elastin and the direct and indirect effects
of elastolysis as well as other novel properties of elastases.
9.2 Elastin
The mechanical properties of many tissues, including the lungs, large arteries,
ovaries, tendons, and skin, are determined by the matrix that composes them. Elastic
fibers are a unique component in those organs that allow for a more uniform
distribution of stress along tissue, storage of energy, and maintenance of form.
Elastic fibers are key to repeated stretch and recoil of the organs mentioned above.
They are formed during development and persist with minimal turnover throughout
adulthood. Their synthesis is complicated, and destruction or dysfunction of these
fibers has been linked to several adult diseases. Furthermore, the complexity of
structure and assembly makes the repair of these fibers difficult leading to perma-
nent, progressive disease.
9.2.1 Elastic Fiber Components
Elastic fibers are the largest structures found in the extracellular matrix. They are
primarily composed of two components, elastin and microfibrils, with several asso-
ciated proteins that further compose the fiber. Elastin is the primary component
(~90%). It is formed by the cross-linking of a monomeric secreted form of the protein
called tropoelastin (Sandberg et al.
1971
). This cross-linking forms an amorphous
elastin polymer that comprises the core of the fiber. The second components, the
microfibrils, are small 10-15 nm fibers that are composed primarily by fibrillins
(Wagenseil and Mecham
2007
). The microfibrils are felt to provide a scaffold for the
tropoelastin cross-linking and for the further cross-linking of elastin to itself by lysyl
oxidase enzymes (Csiszar
2001
; Lucero and Kagan
2006
). In addition to the micro-
fibrils, multiple proteins associate with the either the fibrils or the elastin itself (see
below). They are found both within and surrounding the elastin core.
