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Buckling Reduces eNOS Production and Stimulates Extracellular Matrix Remodeling in Arteries in Organ Culture

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Abstract

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.

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Acknowledgments

The authors thank Granzins Meat Market at New Braunfels, TX, Watark at Poth, TX, and the Pathology Lab at UTHSCSA for their help in this work. This study was supported by Grant HL095852 from the National Heart, Lung, and Blood Institute. It was also partially supported by HHSN 268201000036C (N01-HV-00244) for the San Antonio Cardiovascular Proteomics Center from the National Heart, Lung, and Blood Institute and partially supported by National Natural Science Foundation of China through Grant 11229202.

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Authors and Affiliations

  1. Department of Mechanical Engineering, The University of Texas at San Antonio, San Antonio, TX, 78249, USA

    Yangming Xiao, Qin Liu & Hai-Chao Han

  2. Institute of Mechanobiology & Medical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China

    Hai-Chao Han

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  1. Yangming Xiao
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Correspondence to Hai-Chao Han.

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Associate Editor Jane Grande-Allen oversaw the review of this article.

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Xiao, Y., Liu, Q. & Han, HC. Buckling Reduces eNOS Production and Stimulates Extracellular Matrix Remodeling in Arteries in Organ Culture. Ann Biomed Eng 44, 2840–2850 (2016). https://doi.org/10.1007/s10439-016-1571-0

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