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

血流动力学与血管内皮超微结构和功能关系的研究

• 批准号: 01480248
• 负责人: INOUE Michitoshi
• 金额: $ 4.22万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480248/
• 关键词: Atherosclerosis; Shear Stress; Doppler Velocimeter; Endothelial Cells; Microfilaments; Hypercholesterolemia; Intimal Lesions; atherosclerosis; endothelial cells; Shear Stress; Doppler; hypercholesterolemia

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.

为了将体内低剪切应力条件、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。剪切应力是根据用 80 通道 20 MHz 脉冲多普勒速度计获得的数据重建的瞬时速度剖面来计算的。内皮微丝束的量以透射电子显微照片上填充有微丝的积分面积与内皮细胞总面积的比率(F/C)来评价。比较了三个部位：狭窄近端 10 毫米 (PROX)、紧邻狭窄上游 (ST) 和紧邻狭窄远端 (DISY)。与 PROX 相比，ST 处的剪切应力增加，DIST 处的剪切应力减少。剪切应力和 F/C 之间呈正相关（r=0.94，p<0.01）。内膜斑块仅在紧邻狭窄远端形成，此处剪切应力明显较低。我们还开发了体外剪切应力加载仪器来研究可变剪切应力条件下各种细胞反应的变化。因此，低剪切应力条件可能会减弱内皮微丝束的形成，并可能在致动脉粥样硬化的条件下促进内膜斑块的形成。

项目成果

Uematsu,M.: "Reduction of endothelial microfilament bundles in the lowーshear region of the canine aorta Association with intimal plaque formation in hypercholesteroemia" Arteriosclerosis and Thrombosis. 11. 107-115 (1991)

Uematsu, M.：“犬主动脉低剪切区域内皮微丝束的减少与高胆固醇血症中内膜斑块形成的关联”《动脉硬化和血栓形成》11. 107-115 (1991)。

Uematsu, M., Kitabatake, A., Tanouchi, J., Ishihara, K., Fujii, K., Yoshida, Y., Doi, Y., Kamada, T.: "Low shear stress reduces endothelial microfilament bundles and induces intimal plaque formation in hypercholesterolemic canine aorta." Circulation. 80(S

Uematsu, M.、Kitabatake, A.、Tanouchi, J.、Ishihara, K.、Fujii, K.、Yoshida, Y.、Doi, Y.、Kamada, T.：“低剪切应力会减少内皮微丝束并诱导

Uematsu, M., Kitabatake, A., Tanouchi, J., Doi, Y., Masuyama, T., Fujii, K., Yoshida, Y., Ito, H., Ishihara, K., Hori, M., Inoue, M., Kamada, T.: "Reduction of endothelial microfilament bundles in the low shear region of the canine aorta. Association with

植松 M.、北竹 A.、田内 J.、土井 Y.、增山 T.、藤井 K.、吉田 Y.、伊藤 H.、石原 K.、堀 M.、

Uematsu,M.: "Low shear stress reduces endothlial microfilaments and induces intimal plaque formation in hypercholesterolemic canine aorta." Circulation. 80(Suppl.II). II-556 (1989)

Uematsu,M.：“低剪切应力会减少内皮微丝，并诱导高胆固醇血症犬主动脉内膜斑块的形成。”

Uematsu,M.: "Low Shear Stress Reduces Endothelial Microfilaments and Induces Intimal Plaque Formation in Hypercholesterolemic Canine Aorta" Circulation (Supplement II). 80. II-556 (1989)

Uematsu,M.：“低剪切应力减少内皮微丝并诱导高胆固醇血症犬主动脉内膜斑块形成”循环（补充II）。