Recombinant human thrombomodulin inhibits arterial neointimal hyperplasia after balloon injury Jian-ming Li, MD, Michael J Singh, MD, Mazen Itani, MD,

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Recombinant human thrombomodulin inhibits arterial neointimal hyperplasia after balloon injury Jian-ming Li, MD, Michael J Singh, MD, Mazen Itani, MD, Calin Vasiliu, MD, Gregory Hendricks, PhD, Stephen P Baker, MScPH, John E Hale, PhD, Michael J Rohrer, MD, Bruce S Cutler, MD, Peter R Nelson, MD Journal of Vascular Surgery Volume 39, Issue 5, Pages 1074-1083 (May 2004) DOI: 10.1016/j.jvs.2003.12.030

Fig 1 Microphotographs of cross-section of rabbit femoral artery show normal artery (A, B), 4-day post–balloon injury in buffer control group (C) and rTM infusion group (D), and 2-week post–balloon injury in control group (E) and rTM group (F) (hematoxylin-eosin; original magnification ×5 and ×25). Journal of Vascular Surgery 2004 39, 1074-1083DOI: (10.1016/j.jvs.2003.12.030)

Fig 2 Neointima of cross-section of balloon-injured rabbit femoral artery stained with hematoxylin-eosin. Degree of neointima was measured with digital imaging computerized planimetry, and calculated according to intima-media ratio (A) and lumen–whole artery ratio (B). P < .0001, recombinant thrombomodulin (rTM) vs control, 4 vs 2 weeks (A). Journal of Vascular Surgery 2004 39, 1074-1083DOI: (10.1016/j.jvs.2003.12.030)

Fig 3 Inflammatory cell adhesion and infiltration at 7 days post–balloon injury in rabbit femoral artery. Inflammatory cells were counted in cross sections of three segments (proximal, middle, distal) of six arteries in each group stained with hematoxylin-eosin, with light microscopy at 400× and 1000× magnification. Data for neutrophil adhesion and infiltration are depicted as mean ± SEM. rTM, Recombinant thrombomodulin. Journal of Vascular Surgery 2004 39, 1074-1083DOI: (10.1016/j.jvs.2003.12.030)

Fig 4 Representative immunohistochemical and immunohistofluorescence stained cross sections of 7-day post–balloon injured rabbit femoral arteries. Neutrophils are identified with monoclonal antibody MAC805. Color was developed with DAB stain (left images) or rhodamine red (right images) for control arteries (A) and recombinant human thrombomodulin–treated arteries (B). Similar images were obtained after staining for macrophages (not shown). Journal of Vascular Surgery 2004 39, 1074-1083DOI: (10.1016/j.jvs.2003.12.030)

Fig 5 Representative scanning electron microphotographs of cross section of 7-day post–balloon-injured rabbit femoral arteries in 1-day treatment group. Buffer control arteries (A) versus recombinant human thrombomodulin–treated arteries (B) (original magnification ×1000.) Journal of Vascular Surgery 2004 39, 1074-1083DOI: (10.1016/j.jvs.2003.12.030)

Fig 6 Representative scanning electron microscope (A, C) and transmission electron microscope (B, D) microphotographs of cross sections of 7-day post–balloon-injured rabbit femoral arteries in 3-day treatment group. Buffer control arteries (A, ×1000; B, ×15,000) versus recombinant human thrombomodulin–treated arteries (C, ×1000; D, ×15,000). Journal of Vascular Surgery 2004 39, 1074-1083DOI: (10.1016/j.jvs.2003.12.030)