Biomedical Engineering Reference
In-Depth Information
13.5.2 Deformation
The different microstructural components in the vessel wall have different mechanical properties and
take up loads at different stress levels. Changes in the structure and organization of the vessel constitu-
ents under different mechanical loading conditions have been observed in a nondestructive manner
by two-photon excitation microscopy. Zoumi et al. monitored the effect of transmural pressure (0, 30,
and 180 mmHg) on excised porcine coronary artery microstructure [41]. With increasing pressure, the
fibers became thinner and more elongated. These investigators concluded that the vessel wall is com-
pressed during pressurization, while the elastic lamina is circumferentially stretched. Collagen fiber
width, measured by SHG, was ~3, 3.6, 1.3, and 0.9 μm, in the zero-stress (radially cut no-load vessel),
no-load, 30 mmHg distension, and 180 mmHg distension, respectively. Interestingly, two-photon exci-
tation microscopy revealed that, with 30 mmHg distension, the fibers were thinner toward the lumen
and became thicker toward the outer wall of the vessel, suggesting that the intimal-medial portion of
the vessel takes up more of the load than the adventitia. The applied pressure had a more uniform effect
throughout the vessel wall at 180 mmHg distension, however, as thin fibers were observed to span the
entire wall thickness.
Megens et al. investigated pressure-induced changes in transmural collagen and elastin organization
in large elastic and small muscular arteries mounted in a perfusion chamber [32]. After increasing the
transmural pressure from 0 to 80 mmHg, the carotid artery thickness decreased from ~57 to ~33 μm,
and the elastic laminae appeared to unfold. Collagen imaged by SHG was tortuous in mounted, pressur-
ized elastic arteries (carotid), but appeared more stretched out in similarly mounted muscular arteries
(uterine).
13.6 investigations of LDL interactions with the Vascular Wall
Low-density lipoprotein (LDL) retention in the arterial wall plays a pivotal role in the initiation and
progression of cardiovascular heart disease. The initial step in atherosclerotic lesion formation is cur-
rently thought to involve LDL binding to ECM components (proteoglycans) that are associated with
collagen and elastin [48]. During atherosclerotic lesion development, increasing amounts of LDL and
LDL-derived cholesterol accumulate in the extracellular space, and in macrophages that ingest matrical
LDL. The lipid-rich necrotic core characteristic of advanced lesions renders the vessel prone to rup-
ture and thrombosis formation, with consequent risk of myocardial infarction, stroke, and death. Thus,
the interaction of LDL with vascular wall components is a subject of great interest in cardiovascular
research. Nonlinear optical microscopy technologies provide powerful tools to study these interactions
both in situ and in vivo . Endogenous LDL in arterial cells and extracellular matrix can be imaged by
CARS microscopy, while exogenously added fluorescent-tagged LDL can be imaged by two-photon exci-
tation microscopy.
Our laboratory has used multimodal nonlinear microscopy to identify the atherosclerosis-prone
anatomical sites and arterial components that bind exogenous fluorescent LDL. Based on SHG, Kwon
et  al. found that collagen fibrils are circumferentially organized into a knotted ring surrounding
atherosclerosis-prone intervertebral, aortic arch, and coronary artery branch points (see Figure 13.8)
[39]. Quantification of superficial collagen content by SHG revealed a 24% increase in collagen den-
sity in aortic branch regions relative to the aortic-free wall. Examination of elastin autofluorescence
revealed that, unlike the free wall, the branch points lack an elastin layer, thus exposing collagen/
proteoglycan complexes. As assessed by two-photon microscopy, (i) the luminal elastin layer limited
penetration of fluorescent-tagged probes, whereas its absence at branch points resulted in extensive
LDL binding; and (ii) fluorescent LDL colocalized with immunostained proteoglycans. These studies
revealed that at atherosclerosis-prone branch points in nondiseased tissue, the absence of a lumi-
nal elastin barrier and the presence of a dense collagen/proteoglycan matrix contribute to increased
retention of LDL.
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