Internal elastic lamina gaps in high-flow induced arterial remodeling are comparable with angiogenesis

高流量诱导的动脉重塑中的内部弹性层间隙与血管生成相当

• 批准号: 14570176
• 负责人: MASUDA Hirotake
• 金额: $ 2.11万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570176/
• 关键词: internal elastic lamina gaps; arterio-venous fistula; blood flow increase; endothelial cell; smooth muscle cell; proliferation; arterial remodeling; bone marrow; 血流; 動脈; リモデリング; 血管新生; 内弾性板; 家兎

High-flow rabbit common carotid arteries remodel as follows (mainly obtained from 2002-2003, but some findings included our previous findings).1.Endothelial cells (ECs) start to proliferate at 1.25-day of high-flow, peaked at 2-day, still high at 3-day, and subside at 4-day2.At 3-day of high-flow, ECs are going to contact with medial smooth muscle cells (SMCs) forming EC-SMC couplings.3.From 3-day to 4-day, focal proliferation of SMCs occurs.4.Internal elastic lamina gaps (IEL-gaps) start to appear at 4-day of high-flow.5.Arterial lumen expands as IEL-gaps expand thereafter.6.At 4-week of high-flow, when high-flow induced arterial remodeling happens, almost 50% lumen surface is IEL-gaps.7.Returning to the normal flow by AVF closure, arterial lumen decreases, but the IEL-gaps are still wide and never disappear.8.SMCs in media migrate into intima through IEL-gaps during flow-decrease induced arterial narrowing to induce intimal thickening (flow-alteration induced intimal thickening).9.Flow-alteration induced intimal thickening occurs in each flow-alteration and it pile up progressively.From 1 to 2, remarkable EC activation occurs with high MMP2, MMP9, MT-MMP, and TIMP. TGF-beta and VEGF increase. Ultrastructural observation revealed that activated ECs are similarly observed in both high-flow loaded arteries and high-flow capillaries. During the formation of EC-SMC couplings, there appear many abluminal cytoplasmic protrusions, which is similar to the sproutings of capillary angiogenesis. In the high-flow induced arterial remodeling, however, almost all the protrusions were capped by SMCs, finally forming EC-SMC couplings. When SMCs proliferate, IEL, which is pinned by the coupling between ECs and SMCs, would be stressed finally to be tore forming IEL-gaps. Therefore we consider that IEL-gaps are comparable with angiogenesis.

高流量兔颈总动脉重塑如下(主要来自2002-2003年，但部分发现包括我们以前的发现)。1.内皮细胞(ECs)在高流量1.25天开始增殖，2天达高峰，3天仍高，4天消退。2.高流量3天，内皮细胞与中层平滑肌细胞接触，形成EC-SMC偶联。3.从3天到4天，内皮细胞开始与中膜平滑肌细胞接触，形成EC-SMC偶联。4.内弹力板间隙(IEL-Gap)在高流量4天开始出现。5.动脉管腔随着IEL-间隙的扩大而扩张。6.在高流量4周，当高流量导致动脉重构时，几乎50%的管腔表面是IEL-Gap。7.AVF闭合使动脉管腔恢复正常，管腔缩小，8.在血流减少引起的动脉狭窄过程中，中膜的SMC通过IEL-间隙向内膜迁移，导致内膜增厚(血流改变诱导的内膜增厚)。9.血流改变引起的内膜增厚在每一次血流改变中都发生并逐渐堆积。从1到2，EC显著活化，MMP2、MMP9、MT-MMPp和TIMP升高。转化生长因子-β和血管内皮细胞生长因子升高。超微结构观察显示，在高流量负荷动脉和高流量毛细血管中均可观察到激活的内皮细胞。在EC-SMC偶联的形成过程中，出现许多开放的胞浆突起，类似于毛细血管的萌发。然而，在高流量诱导的动脉重塑中，几乎所有的突起都被SMC覆盖，最终形成EC-SMC偶联。当SMC增殖时，被ECs和SMC之间的耦合钉扎的IEL最终会被应力撕裂，形成IEL-Gap。因此，我们认为IEL-GAP与血管生成具有可比性。

项目成果

Sho M, Masuda H, et al.: "Subnormal shear stress-induced intimal thickening requires medial smooth muscle cell proliferation and migration"Experimental and Molecular Pathology. 72. 150-160 (2002)

Sho M、Masuda H 等人：“低于正常剪切应力诱导的内膜增厚需要内侧平滑肌细胞增殖和迁移”实验和分子病理学。

Ebina T, Hoshi N, Kobayashi M, Kawamura K, Nanjo H, Sugita A, Sugiyama T, Masuda H, Xu C.: "Physiological angiogenesis in electrically stimulated skeletal muscle in rabbits -Characterization of capillary sprouting by ultrastructural three-dimensional reco

Ebina T、Hoshi N、Kobayashi M、Kawamura K、Nanjo H、Sugita A、Sugiyama T、Masuda H、Xu C.：“电刺激兔子骨骼肌的生理血管生成 - 通过超微结构三维重建表征毛细血管发芽

Masuda H, Kawamura K, Nanjo H, Sho E, Momatsu M, Sugiyama T, Sugita A, Asari Y, Kobayashi M, Ebina T, Hoshi N, Singh TM, Xu C, Zarina CK.: "Ultrastructure of endothelial cells under flow alteration."Microscopy Research and Technique. 60. 2-12 (2003)

Masuda H、Kawamura K、Nanjo H、Sho E、Momatsu M、Sugiyama T、Sugita A、Asari Y、Kobayashi M、Ebina T、Hoshi N、Singh TM、Xu C、Zarina CK.：“流下内皮细胞的超微结构

Ebina T, Kawamura K, Nanjo H, Masuda H, et al.: "Physiological angiogenesis in electrically stimulated skeletal muscle in rabbits Characterization of capillary sprouting by ultrastructural three-dimensional reconstruction study"Pathology International. 52

Ebina T、Kawamura K、Nanjo H、Masuda H 等人：“通过超微结构三维重建研究表征毛细血管萌芽的兔电刺激骨骼肌的生理血管生成”病理学国际。

Ebina T, Masuda H, et al.: "Physiological angiogenesis in electrically stimulated skeletal muscle in rabbits : Characterization of capillary sprouting byultrastructural 3-D reconstruction study"Pathology International. 52. 702-712 (2004)

Ebina T、Masuda H 等人：“兔子电刺激骨骼肌中的生理血管生成：通过超微结构 3-D 重建研究表征毛细血管发芽”国际病理学。