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

为了将体内低切应力条件、内皮微丝束形成和内膜斑块形成联系起来，我们引入了一种高胆固醇血症比格犬的轻度主动脉狭窄。根据80道20 MHz脉冲多普勒测速仪获得的数据重建瞬时速度剖面，计算剪应力。在透射电子显微镜下，用充满微丝的完整面积与内皮细胞总面积之比(F/C)来评价内皮微丝束的数量。比较三个部位：狭窄近端10 mm(PROX)、狭窄上游(ST)和狭窄远端(DISY)。与PROX相比，ST段剪切应力增大，DIST段剪切应力降低。切应力与F/C呈正相关(r=0.94，p&lt；0.01)。内膜斑块仅在狭窄的远侧形成，切应力明显较低。我们还研制了一种体外剪应力加载仪，用于研究不同剪应力条件下细胞响应的变化。因此，在动脉粥样硬化的情况下，低切应力条件可能会减弱内皮细胞微丝束的形成，并可能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.