Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts

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Presentation transcript:

Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts Kazuya Fujinaga, MD, Koji Onoda, MD, PhD, Kiyohito Yamamoto, MD, Kyoko Imanaka-Yoshida, MD, PhD, Motoshi Takao, MD, PhD, Takatsugu Shimono, MD, PhD, Hideto Shimpo, MD, PhD, Toshimichi Yoshida, MD, PhD, Isao Yada, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 128, Issue 3, Pages 357-363 (September 2004) DOI: 10.1016/j.jtcvs.2003.11.015

Figure 1 Elastica van Gieson-stained cross sections (B-D and E-F) and immunostaining for TN-C (H-J) of artery grafts (magnification ×40). A, Diagram of implanted grafts indicating sections examined. B-D, Distal anastomotic stricture site. E-J, Graft body. B, E, H, POD 7. C, F, I, POD 14. D, G, J, POD 28. Arrows indicate internal elastic lamina. POD, Postoperative day. The Journal of Thoracic and Cardiovascular Surgery 2004 128, 357-363DOI: (10.1016/j.jtcvs.2003.11.015)

Figure 2 Neointima/media area ratio in graft body (A) and distal anastomotic site (B). Four sections per animal were selected, and data are mean ± SD of neointima/media area ratio from 5 animals per group at each time point. *Significant difference between PODs 14 and 28 in stricture group (graft body: P < .001; anastomotic site: P < .05). **Significant difference between stricture and non-stricture groups at POD 28 (graft body: P < .01; distal anastomotic site: P < .05). POD, Postoperative day. The Journal of Thoracic and Cardiovascular Surgery 2004 128, 357-363DOI: (10.1016/j.jtcvs.2003.11.015)

Figure 3 Localization of TN-C by in situ hybridization. TN-C mRNA was detected in the media and adventitia at POD 7 (A), and predominantly in the neointima at day 14 (B). Arrows indicate TN-C mRNA-positive cells. Neo, Neointima; med, media; adv, adventitia. The Journal of Thoracic and Cardiovascular Surgery 2004 128, 357-363DOI: (10.1016/j.jtcvs.2003.11.015)

Figure 4 Elastica van Gieson–stained cross sections and immunostaining for TN-C of cilostazol-treated graft bodies at POD 28 (magnification ×40). A, C, Cilostazol-treated grafts. B, D, Vehicle-treated grafts. A, B, Elastica van Gieson–stained sections; C, D, Immunostaining for TN-C. In the cilostazol-treated graft body, neointimal hyperplasia was markedly inhibited and TN-C–positive staining was observed in only a small portion of the media. Arrows indicate internal elastic lamina. The Journal of Thoracic and Cardiovascular Surgery 2004 128, 357-363DOI: (10.1016/j.jtcvs.2003.11.015)

Figure 5 Effect of cilostazol in inhibiting neointimal hyperplasia in artery grafts at POD 28. A, B, Neointima/media area ratio. C, D, PCNA index. A, C, Graft body. B, D, Distal anastomotic site. Four sections per animal were selected, and data are mean ± SD of neointima/media area ratio and PCNA index from 5 animals per group. Significant differences were seen between the cilostazol-treated and vehicle-treated groups (*P < .05). The Journal of Thoracic and Cardiovascular Surgery 2004 128, 357-363DOI: (10.1016/j.jtcvs.2003.11.015)

Figure 6 Reverse transcriptase-polymerase chain reaction analysis of TN-C mRNA expression in cultured SMCs isolated from rat aorta. A, Representative reverse transcriptase–polymerase chain reaction data; lane 1: PDGF-BB + cilostazol; lane 2: PDGF-BB; lane 3: no substance added. B, Quantitative analysis of TN-C mRNA levels. *Significant difference between PDGF-BB–treated and PDGF-BB + cilostazol-treated groups (P < .05). TN-C, Tenascin C; bp, base pair; PDGF, platelet-derived growth factor; NS, not significant. The Journal of Thoracic and Cardiovascular Surgery 2004 128, 357-363DOI: (10.1016/j.jtcvs.2003.11.015)