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三天器官培养中轴向扭转下的动脉重塑

Artery Remodeling Under Axial Twist in Three Days Organ Culture.

作者信息

Wang Guo-Liang, Xiao Yangming, Voorhees Andrew, Qi Ying-Xin, Jiang Zong-Lai, Han Hai-Chao

机构信息

Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

出版信息

Ann Biomed Eng. 2015 Aug;43(8):1738-47. doi: 10.1007/s10439-014-1215-1. Epub 2014 Dec 12.

Abstract

Arteries often endure axial twist due to body movement and surgical procedures, but how arteries remodel under axial twist remains unclear. The objective of this study was to investigate early stage arterial wall remodeling under axial twist. Porcine carotid arteries were twisted axially and maintained for three days in ex vivo organ culture systems while the pressure and flow remained the same as untwisted controls. Cell proliferation, internal elastic lamina (IEL) fenestrae shape and size, endothelial cell (EC) morphology and orientation, as well as the expression of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase-2 (TIMP-2) were quantified using immunohistochemistry staining and immunoblotting. Our results demonstrated that cell proliferation in both the intima and media were significantly higher in the twisted arteries compared to the controls. The cell proliferation in the intima increased from 1.33 ± 0.21% to 7.63 ± 1.89%, and in the media from 1.93 ± 0.84% to 8.27 ± 2.92% (p < 0.05). IEL fenestrae total area decreased from 26.07 ± 2.13% to 14.74 ± 0.61% and average size decreased from 169.03 ± 18.85 μm(2) to 80.14 ± 1.96 μm(2) (p < 0.01), but aspect ratio increased in the twist group from 2.39 ± 0.15 to 2.83 ± 0.29 (p < 0.05). MMP-2 expression significantly increased (p < 0.05) while MMP-9 and TIMP-2 showed no significant difference in the twist group. The ECs in the twisted arteries were significantly elongated compared to the controls after three days. The angle between the major axis of the ECs and blood flow direction under twist was 7.46 ± 2.44 degrees after 3 days organ culture, a decrease from the initial 15.58 ± 1.29 degrees. These results demonstrate that axial twist can stimulate artery remodeling. These findings complement our understanding of arterial wall remodeling under mechanical stress resulting from pressure and flow variations.

摘要

由于身体运动和外科手术,动脉常常承受轴向扭曲,但动脉在轴向扭曲下如何重塑仍不清楚。本研究的目的是调查轴向扭曲下动脉壁的早期重塑情况。将猪颈动脉进行轴向扭曲,并在离体器官培养系统中维持三天,同时压力和流量保持与未扭曲的对照组相同。使用免疫组织化学染色和免疫印迹对细胞增殖、内弹性膜(IEL)窗孔的形状和大小、内皮细胞(EC)的形态和取向,以及基质金属蛋白酶(MMPs)、MMP - 2和MMP - 9以及金属蛋白酶组织抑制剂 - 2(TIMP - 2)的表达进行定量分析。我们的结果表明,与对照组相比,扭曲动脉的内膜和中膜中的细胞增殖均显著更高。内膜中的细胞增殖从1.33±0.21%增加到7.63±1.89%,中膜中的细胞增殖从1.93±0.84%增加到8.27±2.92%(p<0.05)。IEL窗孔的总面积从26.07±2.13%减少到14.74±0.61%,平均大小从169.03±18.85μm²减少到80.14±1.96μm²(p<0.01),但扭曲组的纵横比从2.39±0.15增加到2.83±0.29(p<0.05)。在扭曲组中,MMP - 2的表达显著增加(p<0.05),而MMP - 9和TIMP - 2无显著差异。三天后,与对照组相比,扭曲动脉中的内皮细胞显著伸长。在器官培养三天后,扭曲情况下内皮细胞长轴与血流方向之间的夹角为7.46±2.44度,较初始的15.58±1.29度减小。这些结果表明轴向扭曲可刺激动脉重塑。这些发现补充了我们对由压力和流量变化引起的机械应力下动脉壁重塑的理解。

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