A Study on the Interrelations of the Hemodynamics and the Vascualr Endothelial Ultrastructure and Function

为了使体内低切应力条件、内皮微丝束形成和内膜斑块形成相互关联，我们在高胆固醇血症脂肪喂养的比格犬中引入了轻度主动脉瓣狭窄。剪切应力的计算从瞬时速度剖面重建的数据与80通道20 MHz的脉冲多普勒测速仪。内皮微丝束的量被评价为在透射电子显微照片上填充有微丝束的积分面积与内皮细胞的总面积的比率（F/C）。比较了三个研究中心：狭窄近端10 mm（近端）、狭窄上游（ST）和狭窄远端（DISY）。与PROX相比，ST处的剪切应力增加，DIST处的剪切应力降低。切应力与F/C呈正相关（r=0.94，p<0.01）。内膜斑块仅在狭窄远端形成，此处剪切应力明显较低。我们还开发了一种体外剪切应力加载仪器，以研究在不同的剪切应力条件下各种细胞反应的变化。因此，在致动脉粥样硬化条件下，低剪切应力条件可减弱内皮微丝束的形成，并可促进内膜斑块的形成。

To interrelate low shear stress conditions in vivo, endothelial microfilament bundle formation and intimal plaque formation, we introduced a mild aortic stenosis in hypercholesterolemic fat-fed beagles. Shear stress was calculated from the instantaneous velocity profiles reconstructed from the data obtained with a 80 channel 20 MHz pulsed Doppler velocimeter. The amount of endothelial microfilament bundles was evaluated as the ratio of the integrated area filled with microfilaments to the total area of the endothelial cell (F/C) on transmission electron photomicrographs. Three sites were compared : 10 mm proximal to the stenosis (PROX), immediately upstream from the the stenosis (ST) and immediately distal to the stenosis (DISY). Shear stress was increased at ST and decreased at DIST as compared with PROX. A positive correlation was noted between shear stress and F/C (r=0.94, p<0.01). Intimal plaques were formed exclusively immediately distal to the stenosis, where shear stress was significantly low. We have also developed an in vitro shear stress loading instrument to study the alterations in various cell responses under variable shear stress conditions. Thus, low shear stress conditions may attenuate endothelial microfilament bundle formation and may promote the formation of intimal plaques under atherogenic conditions.