Xiao Yangming, Liu Qin, Han Hai-Chao
Department of Mechanical Engineering, The University of Texas at San Antonio, San Antonio, TX, 78249, USA.
Institute of Mechanobiology & Medical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
Ann Biomed Eng. 2016 Sep;44(9):2840-50. doi: 10.1007/s10439-016-1571-0. Epub 2016 Feb 25.
Artery buckling alters the fluid shear stress and wall stress in the artery but its temporal effect on vascular wall remodeling is poorly understood. The purpose of this study was to investigate the early effect of artery buckling on endothelial nitric oxide synthase (eNOS) expression and extracellular matrix remodeling. Bilateral porcine carotid arteries were maintained in an ex vivo organ culture system with and without buckling while under the same physiological pressure and flow rate for 3-7 days. Matrix metalloproteinase-2 (MMP-2), MMP-9, fibronectin, elastin, collagen I, III and IV, tissue inhibitor of metalloproteinase-2 (TIMP-2), and eNOS were determined using Western blotting and immunohistochemistry. Our results showed that MMP-2 expression level was significantly higher in buckled arteries than in the controls and higher at the inner curve than at the outer curve of buckled arteries, while collagen IV content showed an opposite trend, suggesting that artery buckling increased MMP-2 expression and collagen IV degradation in a site-specific fashion. However, no differences for MMP-9, fibronectin, elastin, collagen I, III, and TIMP-2 were observed among the outer and inner curve sides of buckled arteries and straight controls. Additionally, eNOS expression was significantly decreased in buckled arteries. These results suggest that artery buckling triggers uneven wall remodeling that could lead to development of tortuous arteries.
动脉弯曲会改变动脉中的流体剪应力和壁面应力，但其对血管壁重塑的时间效应却知之甚少。本研究的目的是探讨动脉弯曲对内皮型一氧化氮合酶（eNOS）表达和细胞外基质重塑的早期影响。将双侧猪颈动脉置于体外器官培养系统中，在相同的生理压力和流速下，分别进行有弯曲和无弯曲处理3至7天。使用蛋白质印迹法和免疫组织化学法测定基质金属蛋白酶-2（MMP-2）、MMP-9、纤连蛋白、弹性蛋白、胶原蛋白I、III和IV、金属蛋白酶组织抑制剂-2（TIMP-2）以及eNOS。我们的结果表明，弯曲动脉中MMP-2的表达水平显著高于对照组，且在弯曲动脉的内侧曲线处高于外侧曲线处，而胶原蛋白IV的含量则呈现相反的趋势，这表明动脉弯曲以位点特异性方式增加了MMP-2的表达和胶原蛋白IV的降解。然而，在弯曲动脉的外侧和内侧曲线侧与直的对照之间，未观察到MMP-9、纤连蛋白、弹性蛋白、胶原蛋白I、III和TIMP-2的差异。此外，弯曲动脉中eNOS的表达显著降低。这些结果表明，动脉弯曲会引发不均匀的壁重塑，这可能导致迂曲动脉的形成。
