Effects of Oral Prednisone After Stenting in a Rabbit Model of Established Atherosclerosis
Flavio Ribichini, MD*,
Michael Joner, MD ,
Valeria Ferrero, MD*,
Aloke V. Finn, MD ,
Johanna Crimins, BA,
Gaku Nakazawa, MD,
Eduardo Acampado, DVM,
Frank D. Kolodgie, PhD,
Corrado Vassanelli, MD* and
Renu Virmani, MD,*
* Division of Cardiology of the Università di Verona, Ospedale Civile Maggiore, Verona, Italy
Cardiac Unit, Department of Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts
CVPath Institute, Inc., Gaithersburg, Maryland
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Figure 2 Histologic Sections of the Iliac Arteries 42 Days After Stent Implantation and Bar Graph of Percent Stenosis
(A to C) Sections show low-power (20x, top) and high-power (100/200x, bottom) magnification following Movat Pentachrome staining. Percent stent stenosis is much greater in the control group (A) as compared with prednisone-treated animals (B) and Taxus stents (C). (D) The bar graph shows a significant reduction between the control group and prednisone-treated rabbits (–30%) and Taxus stents (–34%).
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Figure 3 Fibrin Presence in the Iliac Arteries 42 Days After Stent Implantation and Bar Graph for Percentage of Fibrin Area
Photomicrographs showing fibrin deposition around stent struts using Carstair’s stain (A to C) (pink color), stain with antibody against fibrin (D to F) (brown color) and hematoxylin-eosin (G to I) in control animals (A, D, G), prednisone-treated animals (B, E, H) and Taxus stents (C, F, I). Note that maximum fibrin is seen in Taxus stents after 42 days. (J) Bar graph showing significantly greater percentage of fibrin area in Taxus stents compared with control or prednisone-treated animals.
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Figure 4 Inflammation at Luminal Surfaces and Bar Graph for the Heterophils/Eosinophils
Demonstration of luminal eosinophils/heterophils after staining with H&E at high (200x, insets at 400x) magnification. Note, greatest number of eosinophils/heterophils are seen in Taxus stents (C) versus prednisone-treated (B) and control (A) animals. (D) Bar graph demonstrating significant differences in luminal inflammatory cells among treatment groups.
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Figure 5 Bar Graphs of Inflammatory Cytokine Release
Bar graphs representing changes in inflammatory cytokine release among control and prednisone- and Taxus-treated arteries 7 days following stent implantation. Semiquantification of individual cytokines was performed by densitometry analysis and expressed as pixels. Differences were considered significant following comparison with control arteries by analysis of variance with Bonferroni correction (p < 0.25). Prednisone reduced the release of interleukin (IL)-6 (p < 0.02), monocyte chemoattractant protein (MCP)-2 (p < 0.002), MCP-3 (p < 0.009), and tumor necrosis factor (TNF)-alpha (p < 0.01) significantly compared with control subjects, whereas Taxus stents led to a further significant reduction of interleukin (IL)-10 (p < 0.01), IL-13 (p < 0.003), MCP-1 (p < 0.007), and transforming growth factor (TGF)-beta (p < 0.01). *Significance between Taxus and bare-metal stents;  significance between prednisone and bare-metal stent. GRO-a = growth-related oncoprotein-alpha.
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Figure 6 In Vitro Scratch Assay With Human Umbilical Vein Endothelial Cells and the Bar Graph of Cell Density
Representative photomicrographs of scratch injury following treatment with either low serum essential culture media (LSECM) + dimethyl sulphoxide (control) (A), LSECM + prednisone (B), or LSECM + paclitaxel (C) (0.01 µM). Graphic analysis of scratch assay indicates that there is no significant difference between endothelial cell density increase values for the control and prednisone treatment conditions (D). There is a significantly less increase in cell density in the paclitaxel treatment condition (53.68 cells/area ± 12.29) compared with both the control (209.89 ± 32.06) and the prednisone (260.16 ± 51.40) treatment conditions.
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