This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Salzberg, S. P. Articles by Adams, D. H. Search for Related Content PubMed PubMed Citation Articles by Salzberg, S. P. Articles by Adams, D. H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Diabetes

(Circulation. 2006;114:I-302 – I-307.)
© 2006 American Heart Association, Inc.

Myocardial Protection and Vascular Biology

Increased Neointimal Formation After Surgical Vein Grafting in a Murine Model of Type 2 Diabetes

Sacha P. Salzberg, MD; Farzan Filsoufi, MD; Anelechi Anyanwu, MD; Kai von Harbou, MD; Eva Karlof, MD; Alain Carpentier, MD, PhD; Hayes M. Dansky, MD; David H. Adams, MD

From the Department of Cardiothoracic Surgery (S.P.S., F.F., A.A., K.v.H., E.K., A.C., D.H.A.), Mount Sinai Medical Center, New York, NY; Division of Cardiology (H.M.D.), Columbia University, New York, NY.

Correspondence to Sacha P. Salzberg, Department of Cardiothoracic Surgery, Mount Sinai Medical Center, 1190 Fifth Ave, Box 1028, NY, NY 10029. E-mail sacha.salzberg{at}gmail.com

Background— Diabetes is an independent risk factor for the development of neointimal hyperplasia and subsequent vein graft failure after coronary or peripheral artery bypass grafting. We evaluate a new mouse model of surgical vein grafting to investigate the mechanisms of neointimal formation in the setting of type 2 diabetes.

Methods and Results— Surgical vein grafts were created by inserting vein segments from age-matched C57BL/KsJ wild-type mice into the infra-renal aorta of lepr^db/db diabetic and C57BL/KsJ wild-type mice. Mice were euthanized &4 weeks later, and vein grafts were analyzed using morphometric and immunohistochemical techniques. A significant increase in neointimal formation was noted in lepr^db/db mice (139±64 versus 109±62 mm²; P=0.008) after 4 weeks. This difference was mainly secondary to an increase in collagen formation within the lesion in the vein grafts from lepr^db/db mice (0.53±0.4 versus 0.44±0.05; P<0.001), whereas only slight increases (P=not significant) in alpha actin-stained smooth muscle cells were noted in the lepr^db/db mice.

Conclusion— We established a new physiologically relevant model of surgical vein grafting in mice. In this report, type 2 diabetes was associated with significant increase in extracellular matrix deposition in addition to increased smooth muscle cell deposition. This new model may allow mechanistic studies of cellular and molecular pathways of increased neointimal formation in the setting of diabetes.

Key Words: coronary artery disease • diabetes • mouse • neointima • surgery