Reduction of endothelial microfilament bundles in the low-shear region of the canine aorta. Association with intimal plaque formation in hypercholesterolemia.
To interrelate in vivo wall shear stress, endothelial microfilament bundle formation, and atherosclerosis localization, we used a mild abdominal aortic stenosis in 11 beagles to produce a range of wall shear stresses above and below the constriction. Six of the beagles were fed standard animal chow supplemented with 5% cholesterol and 10% coconut oil. Wall shear stresses, endothelial microfilament bundles, and intimal plaque localization were assessed along the stenosed aorta. Shear stress was determined in vivo from the near-wall velocity profiles with a 20-MHz, 80-channel, multigate Doppler velocimeter. Content of the microfilament bundles was quantified by planimetry of transmission electron photomicrographs. After 6 weeks, mean shear stress was higher immediately upstream from the throat of the stenosis than at the proximal site (46.1 +/- 7.3 dynes/cm2 versus 24.0 +/- 6.2 dynes/mc2, p less than 0.001) and was significantly lower immediately distal to the stenosis than at the proximal site (9.4 +/- 0.3 dynes/cm2, p less than 0.01). The microfilament bundle content increased immediately upstream from the throat of the stenosis and decreased immediately distal to the stenosis compared with the proximal site in both normocholesterolemic and hypercholesterolemic fat-fed beagles. Intimal plaques formed exclusively immediately distal to the stenosis in the hypercholesterolemic beagles. These findings suggest that a low shear-stress environment attenuates endothelial microfilament bundle formation, thus leading to a predilection for the initiation of atherosclerosis in atherogenic conditions such as hypercholesterolemia.
Uematsu
M
M
First Department of Medicine, Osaka University School of Medicine, Japan.
Kitabatake
A
A
Tanouchi
J
J
Doi
Y
Y
Masuyama
T
T
Fujii
K
K
Yoshida
Y
Y
Ito
H
H
Ishihara
K
K
Hori
M
M
D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D000818:Animals; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D001783:Blood Flow Velocity; D004285:Dogs; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006937:Hypercholesterolemia / Q000000981:diagnostic imaging / Q000473:pathology*; D008854:Microscopy, Electron; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D014463:Ultrasonography