Kirstyn E Brownson1, Ramak Khosravi2, Shin-Rong Lee1, Kimberly Goldstein2, Toshihiko Isaji1, Shun Ono1, Clinton D Protack1, Jay D Humphrey3, Alan Dardik4. 1. Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut; Department of Surgery, Yale University School of Medicine, New Haven, Connecticut. 2. Department of Biomedical Engineering, Yale University School of Engineering, New Haven, Connecticut. 3. Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut; Department of Biomedical Engineering, Yale University School of Engineering, New Haven, Connecticut. 4. Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut; Department of Surgery, Yale University School of Medicine, New Haven, Connecticut; Department of Surgery, VA Connecticut Healthcare Systems, West Haven, Connecticut. Electronic address: alan.dardik@yale.edu.
Abstract
BACKGROUND: An arteriovenous fistula (AVF) exposes the outflow vein to arterial magnitudes and frequencies of blood pressure and flow, triggering molecular pathways that result in venous remodeling and AVF maturation. It is unknown, however, how venous remodeling, that is lumen dilation and wall thickening, affects venous mechanical properties. We hypothesized that a fistula is more compliant compared with a vein because of altered contributions of collagen and elastin to the mechanical properties. METHODS: Ephb4+/- and littermate wild-type (WT) male mice were treated with sham surgery or needle puncture to create an abdominal aortocaval fistulae. The thoracic inferior vena cava was harvested 3 wk postoperatively for mechanical testing and histological analyses of collagen and elastin. RESULTS: Mechanical testing of the thoracic inferior vena cava from Ephb4+/- and WT mice showed increased distensibility and increased compliance of downstream veins after AVF compared with sham. Although Ephb4+/- veins were thicker than WT veins at the baseline, after AVF, both Ephb4+/- and WT veins showed similar wall thickness as well as similar collagen and elastin area fractions, but increased collagen undulation compared with sham. CONCLUSIONS: Fistula-induced remodeling of the outflow vein results in circumferentially increased distensibility and compliance, likely due to post-translational modifications to collagen. Published by Elsevier Inc.
BACKGROUND: An arteriovenous fistula (AVF) exposes the outflow vein to arterial magnitudes and frequencies of blood pressure and flow, triggering molecular pathways that result in venous remodeling and AVF maturation. It is unknown, however, how venous remodeling, that is lumen dilation and wall thickening, affects venous mechanical properties. We hypothesized that a fistula is more compliant compared with a vein because of altered contributions of collagen and elastin to the mechanical properties. METHODS:Ephb4+/- and littermate wild-type (WT) male mice were treated with sham surgery or needle puncture to create an abdominal aortocaval fistulae. The thoracic inferior vena cava was harvested 3 wk postoperatively for mechanical testing and histological analyses of collagen and elastin. RESULTS: Mechanical testing of the thoracic inferior vena cava from Ephb4+/- and WT mice showed increased distensibility and increased compliance of downstream veins after AVF compared with sham. Although Ephb4+/- veins were thicker than WT veins at the baseline, after AVF, both Ephb4+/- and WT veins showed similar wall thickness as well as similar collagen and elastin area fractions, but increased collagen undulation compared with sham. CONCLUSIONS:Fistula-induced remodeling of the outflow vein results in circumferentially increased distensibility and compliance, likely due to post-translational modifications to collagen. Published by Elsevier Inc.
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