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J Thorac Cardiovasc Surg 2000;119:983-989
© 2000 The American Association for Thoracic Surgery

Surgery For Acquired Cardiovascular Disease

Inducible expression of basic transcription element–binding protein 2 in proliferating smooth muscle cells at the vascular anastomotic stricture

From the Second Department of Surgery^a and the Second Department of Internal Medicine,^b Gunma University School of Medicine, Maebashi, Gunma, Japan.

Supported by a grant-in-aid of the Ministry of Education, Science, and Culture of Japan.

Address for reprints: Ryozo Nagai, MD, Second Department of Internal Medicine, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi City, Gunma 371-8511, Japan.

Objective: The proliferation of vascular smooth muscle cells surrounding a suture line is an important factor in the development of anastomotic stricture that is frequently seen after coronary artery bypass grafting. The aim of this study was to investigate the time course of intimal thickening and to examine the expression of the molecular marker of smooth muscle cell activation surrounding the suture line.
Methods: Longitudinal aortotomy was performed in the abdominal aorta of rats. The rats were put to death 1, 2, 4, and 8 weeks after aortotomy, and the percentage of the lumen occluded by intimal thickening was calculated. All tissues were stained with antibodies against basic transcription element– binding protein 2, human cyclin-dependent kinase (cdk4), and Sp1 for immunohistochemistry. Basic transcription element–binding protein 2 is a transcription factor that is involved in phenotypic modulation of vascular smooth muscle cells. Cdk4 represents a marker for G₁ phase of the cell cycle. Sp1 is a transcription factor known to be expressed in a variety of tissues. Basic transcription element–binding protein 2 messenger RNA expression was confirmed by means of reverse transcriptase–polymerase chain reaction.
Results: We noted significant thickening of the intimal layer 1 week after aortotomy. Immunohistochemistry demonstrated that smooth muscle cells in the neointima were strongly positive for basic transcription element–binding protein 2 and human cyclin-dependent kinase 4, which peaked 2 weeks after aortotomy. Basic transcription element–binding protein 2 expression was closely associated with human cyclin-dependent kinase 4 expression in the neointima, although Sp1 was not. Basic transcription element–binding protein 2 messenger RNA levels were significantly up-regulated early after aortotomy.
Conclusion: The experimental rat aortotomy model is useful to investigate the proliferation of vascular smooth muscle cells around the suture line. Moreover, our results suggest the possible role of basic transcription element–binding protein 2 in the development of vascular anastomotic strictures.

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