Disturbed shear stress reduces Klf2 expression in arterial‐venous fistulae in vivo

Physiological Reports

Kota Yamamoto¹  Clinton D. Protack²  Go Kuwahara²  Masayuki Tsuneki²  Takuya Hashimoto²  Michael R. Hall²  Roland Assi²  Kirstyn E. Brownson²  Trenton R. Foster²  Hualong Bai²  Mo Wang²  Joseph A. Madri² 

[1] Veterans Affairs Connecticut Healthcare Systems, West Haven, Connecticut;Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut

关键词: Arteriovenous fistula;    disturbed flow;    kruppel‐like factor 2;    laminar flow;    shear stress;   

DOI  :  10.14814/phy2.12348

来源: Wiley

【 摘 要 】

Abstract

Laminar shear stress (SS) induces an antiproliferative and anti-inflammatory endothelial phenotype and increases Klf2 expression. We altered the diameter of an arteriovenous fistula (AVF) in the mouse model to determine whether increased fistula diameter produces disturbed SS in vivo and if acutely increased disturbed SS results in decreased Klf2 expression. The mouse aortocaval fistula model was performed with 22, 25, or 28 gauge needles to puncture the aorta and the inferior vena cava. Duplex ultrasound was used to examine the AVF and its arterial inflow and venous outflow, and SS was calculated. Arterial samples were examined with western blot, immunohistochemistry, and immunofluorescence analysis for proteins and qPCR for RNA. Mice with larger diameter fistulae had diminished survival but increased AVF patency. Increased SS magnitudes and range of frequencies were directly proportional to the needle diameter in the arterial limb proximal to the fistula but not in the venous limb distal to the fistula, with 22-gauge needles producing the most disturbed SS in vivo. Klf2 mRNA and protein expression was diminished in the artery proximal to the fistula in proportion to increasing SS. Increased fistula diameter produces increased SS magnitude and frequency, consistent with disturbed SS in vivo. Disturbed SS is associated with decreased mRNA and protein expression of Klf2. Disturbed SS and reduced Klf2 expression near the fistula are potential therapeutic targets to improve AVF maturation.

【 授权许可】

CC BY   
© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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