Biomedical Engineering Reference
In-Depth Information
(increase in number), apoptosis (cell suicide), and migration (often from the media
to subintima) play essential roles in diseases such as aneurysms, atherosclerosis,
and hypertension. Loss of matrix proteins, particularly elastin, similarly plays key
roles in the formation of aneurysms or dissections.
The adventitia, or outer layer, often merges with the perivascular tissue. It
consists primarily of fibroblasts and axially oriented type I collagen, but may
include admixed elastic fibers, nerves, and its own small vasculature, the vasa
vasorum, when the thickness of the wall is too great to allow sufficient transmural
diffusion of oxygen directly from the blood. Fibroblasts are responsible primarily
for regulating the matrix, particularly collagen, but they can migrate, proliferate,
and differentiate. Indeed, there is growing evidence that migrating fibroblasts play
significant roles in many diseases. Nevertheless, the normal adventitia is thought to
serve, in large part, as a protective sheath that prevents over-distension of the
media; like all muscle, smooth muscle contracts maximally at a certain length,
above and below which the contractions are less forceful. Finally, the adventitia is
typically demarcated from the media by an external elastic lamina (except in
cerebral arteries); the media is similarly demarcated from the intima by an internal
elastic lamina, which is a fenestrated, cylindrical sheet of elastin.
Cross-linked elastin is one of the most stable proteins in the body; it endows
vessels with considerable elasticity over finite deformations (e.g., nearly linear
stress response over stretches of 150-200 %) and it helps control the phenotype of
the SMCs. Specifically, cross-linked elastin encourages a quiescent, contractile
phenotype characteristic of maturity. This is in contrast to effects of the elastin
precursor, tropoelastin, which is not cross-linked, contributes little to the structural
integrity, and encourages smooth muscle migration, proliferation, and synthesis of
extracellular matrix, particularly in development. The collagens are the primary
family of structural proteins in the body, with fibrillar types I and III endowing
tissues with significant tensile stiffness. Collagen fibers turn over continuously and
thereby play key roles in homeostasis and remodeling. They can be on the order of
microns in diameter and are often undulated slightly in the normal physiologic
state; they manifest their high stiffness when straightened. Proteoglycans represent
a large class of molecules having diverse functions. Structurally, they tend to be
most important in sequestering water within the tissue, which, as in cells, typically
accounts for *70 % of the total mass. To provide a better idea of relative dis-
tributions of these various constituents, the media of the thoracic aorta (cf. Fig. 1 )
consists of, by dry weight, *37 % collagen, 33 % SMCs, 24 % elastin, and 6 %
other constituents whereas the adventitia consists of *78 % collagen, 9 %
fibroblasts, 2 % elastin, and 11 % other constituents. Nevertheless, each vessel has
different distributions of constituents within each layer and different relative
thicknesses of the media and adventitia; overall structural integrity is thus dif-
ferentially controlled by balances and imbalances in cell and matrix turnover
(Fig. 2 ). For more on vascular ECM and its relation to mechanics, see [ 62 ].
Vascular structure, function, and material properties are dictated by the three
primary cell types of the wall (endothelial, smooth muscle, and fibroblasts) and in
some cases cells from the blood stream (e.g., platelets, monocytes, progenitor
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