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Methods Mouse thoracic aortas (immature n=4, mature n=5) fixed in vivo at physiological pressure via cannula in left ventricle Aorta excised, permeabilised.

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Presentation on theme: "Methods Mouse thoracic aortas (immature n=4, mature n=5) fixed in vivo at physiological pressure via cannula in left ventricle Aorta excised, permeabilised."— Presentation transcript:

1 Methods Mouse thoracic aortas (immature n=4, mature n=5) fixed in vivo at physiological pressure via cannula in left ventricle Aorta excised, permeabilised (Triton X-100) and incubated in ribonuclease EC nuclei (ECn) stained with propidium iodide and viewed en face and stack of optical slices through wall obtained with inverted confocal microscope Individual ECn manually selected in each optical slice and montaged (Fig.2) ECn analysed for length-to-width (LW) ratio and angle of orientation in 8 regions surrounding ostia (Fig.2 inset) HAEMODYNAMIC STRESSES AND WALL STRUCTURE CAN ACCOUNT FOR THE PATTERN OF LIPID DEPOSITION AROUND AORTIC BRANCHES IN MICE A.R. Bond & P.D. Weinberg Physiological Flow Studies Group, Department of Bioengineering, Imperial College London, UK Results We would like to thank the BHF for funding this study Discussion Pattern of nuclear elongation and alignment different to those previously found in rabbits (Al-Musawi et al, 2004) Length-to-width ratios were similar in all regions surrounding ostia (intimal cushion excluded) (P>0.05) Trends similar in young and mature mice (P>0.05) Length-to-width ratios of nuclei on cushion lower than elsewhere around ostia suggesting a region of disturbed flow that could correlate with chevron-shaped lesion distribution (P<0.05) Nuclear angles varied around branch (P<0.05) but angles small compared to those in rabbits Spatial and temporal uniformity of flow patterns correlates with uniformity of lipid deposition patterns in knockout mice References Al-Musawi et al, Atherosclerosis 2004; 172: McGillicuddy et al, Arterioscler Thromb Vasc Biol 2001; 21: Fig 1a,b) En face views of mouse ostia stained for lipid deposition. Note chevron-shaped lesion distribution around ostia in b. Outline of individual ostium marked. Blood flow is from top to bottom. Fig 2) En face montage of propidium iodide stained endothelial cell nuclei, superimposed over wall autofluorescence. Inset: Regions analysed around branch. Blood flow is from top to bottom. Fig 3) En face view of intimal cushion. Blood flow is from top to bottom. Fig 4) Endothelial nuclear length-to-width ratios (indicating shear) and orientations (indicating flow direction) around intercostal branch ostia in mouse aortas Introduction Atherosclerosis has a patchy distribution within arteries Blood flow / haemodynamics may be a crucial factor Difficult to determine flow in vivo under physiological conditions Endothelial cells (EC) can be used as in situ biological flow sensors since they elongate in regions of high wall shear stress and align with flow direction Lesions occur downstream of aortic branch ostia in immature people and rabbits, but upstream at later ages Endothelial nuclei are more elongated (indicating higher shear) downstream of intercostal branch ostia in immature rabbits, but upstream in mature ones (Al-Musawi et al, 2004) Pattern of lipid deposition around intercostal ostia in mouse aorta differs from that in people and rabbits Low density lipoprotein receptor/apolipoprotein E double knockout mice develop lesions surrounding ostia (Fig.1a) Additionally, a chevron-shaped lesion (intimal cushion) is located upstream of many ostia (Fig.1b) (McGillicuddy et al, 2001) ab


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