Acute Aortic Disease.. - Index of

232 Sanz et al.
also decrease wall strength, thus favoring rupture (16–18). Reductions in the
number of smooth muscle cells appear to favor aortic dilatation due to loss of their
metabolic function rather than because of diminished contractile capacity (7).
Collagen abnormalities, such as those seen in Ehlers–Danlos syndrome, are
similarly associated with increased risk of arterial dilatation and dissection (19).
Although conflicting results have been reported, collagen amount seems to be
increased in pathologic aortas, perhaps in an attempt to repair or maintain structural
integrity, although newly synthesized collagen may be defective (20–23).
Elastin and collagen crosslinks, which play a role in filament stabilization, are
also abnormally reduced in aneurysms (23,24).
Other structural proteins may also be involved in aneurysm formation and
predisposition for dissection (7). Fibrillin, abnormal in Marfans’s syndrome, contributes
to the extracellular microfibrillar ultrastructure that serves as the support for
elastin deposition and plays a role in the distribution of shear stress (7,25) Fibulin-5
participates in the regulation of elastic fiber assembly. Its expression is reduced in
subjects with proximal aortic dissection and correlates with the degree of elastin
degeneration (26). Also, peptidases, such as matrix metalloproteinases and elastase,
play a role in elastin and collagen degeneration and aneurysm formation (27–29).
Mural ischemia is probably a significant contributor to the development of
aortic dissection. Whereas the intima and inner media nourish mainly by passive
diffusion from the lumen, the outer layers of large arteries receive their nutrients
through the vasa vasorum (30). Interestingly, the common plane of dissection of
the vessel wall is the outer third of the media, the limit between the two zones
(30,31). Intimal thickening characteristic of atherosclerotic disease may compromise
the nourishment of the inner media. Similarly, a decrease in number or function
of the vasa vasorum results in ischemic medial necrosis, morphologic changes
in collagen and elastin fibers of the outer media, increases in collagen content, and
enhanced aortic stiffness at various levels of mechanical stress (32,33). Ischemia
promotes inhomogeneity in the transmural mechanical properties, resulting in
increased interlayer shear stress that may favor dissection (33). Alterations in vasa
vasorum functionality take place, for example, in arterial hypertension (34).
Hemodynamic Factors
In a cylindrical tube, circumferential stress is determined by Laplace’s law (35):
T ≈ Pt × R/μ,
where T is the circumferential wall tension, P t the transmural wall pressure (intravascular
minus extravascular wall pressure), R the radius of the vessel, and μ the
wall thickness. Although there are ethnic and interindividual differences in aortic
wall thickness that may influence wall tension (36), transmural pressure and the
vessel diameter are considered the most important determinants. It is clear from
Laplace’s law that stress will increase proportionally to the arterial diameter,
which explains why aneurysms rupture more frequently than nondilated segments.