Biomedical Engineering Reference
In-Depth Information
FIgurE 13.8
(
See color insert
.) LDL binds to collagen- and proteoglycan-rich, elastin-poor aortic branch
points. (a) Three-dimensional surface reconstructions of atherosclerosis-susceptible intervertebral branch points
along the mouse thoracic aorta revealing with a ring of exposed collagen immediately surrounding the ostia.
Elastin autofluorescence is red; collagen SHG is green. Scale bar = 50 μm. (b) LDL binding along the mouse aorta
detected by epifluorescence. Alexa 647-tagged LDL bound extensively to a circular region around interverte-
bral branch points. Scale bar = 500 μm. Zoom scale bar = 100 μm. (c) Colocalization analysis of LDL binding
at porcine coronary arterial branch points. Two-photon image of LDL (red) colocalization with immunolabeled
proteoglycans (green). (Adapted from Kwon, G. P. et al. 2008.
Circulation
117:2919-2927. With permission from
Wolters Kluwer.)
Further, two-photon microscopic studies of nondiseased aortic wall microstructure led to the
discovery of a heretofore unidentified anatomical structure, the renal artery ostial diverter (see
Figure 13.9) [42]. In these studies, maximum projection images of adjacent z-stacks (~180 μm deep)
were tiled together to form a high-resolution, low-magnification, composite
en face
image of the entire
renal ostium (~1 mm
2
area). The renal flow diverter was initially identified, by SHG imaging, as a
crescent-shaped region of increased collagen density on the caudal (downstream) side of the aortic
entrance to porcine renal artery (renal ostium). Subsequent histological analysis revealed the renal
diverter to be a knife-like, intimal collagenous cap on top of a thickened tunica media, which together
form a process that protrudes into the aorta. High-resolution color Doppler ultrasound studies
in vivo
confirmed that the structure serves to divert arterial blood flow into the renal artery. Interestingly,
the anatomical site where the diverter resides has been shown to be the site of initiation of renal arte-
rial atherosclerosis. Two-photon microscopy revealed that, relative to the cranial (upstream side) of
the renal ostium, the diverter has a thin luminal elastin layer, and a 25-fold increase in fluorescent
LDL binding, consistent with our observations at other atherosclerosis-prone arterial branch points
