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Tumor necrosis factor-α and the early vein graft

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1 Tumor necrosis factor-α and the early vein graft
Zhihua Jiang, MD, PhD, Ankur Shukla, BS, Brett L. Miller, BS, Derek R. Espino, BS, Ming Tao, MD, Scott A. Berceli, MD, PhD, C. Keith Ozaki, MD  Journal of Vascular Surgery  Volume 45, Issue 1, Pages (January 2007) DOI: /j.jvs Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

2 Fig 1 Bilateral vein graft model with differential flow environments. Left panel, External jugular vein interposition in the common carotid artery was constructed with cuffed anastomosis. Right panel, All distal branches except the occipital artery were ligated to decrease the ipsilateral flow and gain compensatory increase in the blood flow on the opposite side. Adapted from Am J Physiol Heart Circ Physiol 2004;286:H Used with permission. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

3 Fig 2 A, Shear stress, B development of neointima, and C expression of tumor necrosis factor-α (TNF-α) messenger RNA (mRNA) in low-flow and high-flow vein grafts over time. Both time and flow were identified as independent factors by two-way repeated measures analysis of variance (P < .001 for all three end points). Data are presented as means ± SEM. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

4 Fig 3 Left panel, Pegylated soluble tumor necrosis factor receptor I (PEG sTNF-RI) immunoreactivity in a long-term treated graft (no counterstain). PEG sTNF-RI colocalizes with cells in the neointima. Arrowheads indicate internal elastic lamina. Right panel, Negative control (where the antibody was replaced with antibody dilution serum) was completely negative, suggesting the specificity of anti-PEG sTNF-RI immunostaining. Enzymatic 3,3’-diaminobenzidine precipitation was employed to visualize the specific positive staining (original × 400). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

5 Fig 4 Summary of flow rate at the time of harvest, neointimal thickness, and internal elastic lamina (IEL) length for vein grafts with short-term (daily dosing for the first 5 postoperative days of a 28-day observation period) and long-term (daily dosing from 1 day preoperatively until the end of the 14-day observation) anti-tumor necrosis factor-α treatment. No significant difference was detected for both low-flow and high-flow grafts between treated vein grafts and vehicle controls. PEG sTNF-RI, Pegylated soluble tumor necrosis factor receptor 1. Data are presented as means ± SEM. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

6 Fig 5 Upper panel, Density of TUNEL (A) and Ki-67 (B) positive cells in low-flow vein grafts with long-term antitumor necrosis factor-α treatment. Data are presented as means ± SEM. Lower panel, Representative images for TUNEL and Ki-67 from the same animal. The treated vein grafts tended to have more TUNEL-positive and less Ki-67–positive cells in the neointima, but these differences are not statistically significant. PEG sTNF-R1, Pegylated soluble tumor necrosis factor receptor 1; TUNEL, terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

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