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

Zakar H. Mnjoyan, Dennis Doan, Jimi Lynn Brandon, Kumar Felix, Christy L. Sitter, Ajay A. Rege, Tommy A. Brock, Ken Fujise

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Post-angioplasty 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.

Original languageEnglish (US)
Pages (from-to)H2276-H2284
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5
StatePublished - May 2008


  • 5-Bromo-2′-deoxyuridine
  • Carotid artery injury
  • Harlan rats
  • Sasco rats
  • Terminal deoxynucleotidyl transferase-deoxyuridine nick-end labeling
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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