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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/H2276    most recent ajpheart.91527.2007v1 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mnjoyan, Z. H. Articles by Fujise, K. Search for Related Content PubMed PubMed Citation Articles by Mnjoyan, Z. H. Articles by Fujise, K.

The critical role of the intrinsic VSMC proliferation and death programs in injury-induced neointimal hyperplasia

¹Research Center for Cardiovascular Diseases, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston; ²Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Smithville; ³Encysive Pharmaceuticals, Houston; and ⁴Division of Cardiology, Department of Internal Medicine, Medical School, University of Texas Health Science Center at Houston, Houston, Texas

Submitted 27 December 2007 ; accepted in final form 6 March 2008

Postangioplasty and in-stent restenosis remain ominous problems in percutaneous coronary intervention where good animal models of restenosis proneness and resistance are needed. We accidentally discovered that the carotid arteries (CAs) of the Harlan and Sasco substrains of Sprague-Dawley rats display drastically different restenosis phenotypes following balloon-induced endothelial denudation. When subjected to balloon injury, Sasco CAs exhibited significantly larger neointimal mass than did Harlan CAs at both days 14 and 32, as evidenced by a higher intima-to-media ratio and a greater number of intimal cells in Sasco CAs. This was due to a greater cell proliferation and to a less vigorous apoptosis of Sasco neointima, as assessed by 5-bromo-2'-deoxyuridine and terminal deoxynucleotidyl transferase-deoxyuridine nick-end labeling staining, respectively. At a cellular level, whereas vascular smooth muscle cells (VSMCs) isolated from Sasco and Harlan CAs were identical in morphology and in propensity to migrate, Sasco VSMCs proliferated more robustly and died far less, suggesting that under the exact same microenvironment, Sasco and Harlan VSMCs respond to growth and noxious stimuli in a drastically different fashion and that Sasco's significantly more robust neointimal proliferation after vascular injury in vivo can be accounted for by these intrinsic differences in VSMCs of these substrains in vitro. Sasco and Harlan Sprague-Dawley rats as well as VSMCs from these rats will prove to be powerful tools to study genes involved in the pathogenesis of restenosis.

Harlan rats; Sasco rats; carotid artery injury; vascular smooth muscle cells; terminal deoxynucleotidyl transferase-deoxyuridine nick-end labeling; 5-bromo-2'-deoxyuridine