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Open Access Ribonucleotide Reductase Inhibitors Reduce Atherosclerosis in a Double-Injury Rabbit Model

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Abstract:

Atheroproliferative disorders such as atherosclerosis are an important health problem and one of the leading causes of morbidity and mortality in the United States. Minimally invasive therapeutic procedures, including angioplasty with stent deployment, are used frequently for obstructive coronary artery disease. However, restenosis, a proliferative vascular response, is a common sequela to this procedure. The current study investigated the effect of inhibiting ribonucleotide reductase (RR), an enzyme necessary for cellular proliferation, in an attempt to ameliorate the proliferative response. Two RR inhibitors, didox and hydroxyurea, were chosen for their potent antiproliferative properties. Studies were carried out by using a double-injury rabbit model, in which endothelial denudation was followed by the administration of a high-fat diet. At 4 wk after initial endothelial denudation, the developing atherosclerotic lesion was subjected to transluminal balloon dilation to simulate clinical intervention with percutaneous transluminal angioplasty. The degree of restenosis and atheroproliferation was assessed at 8 wk. Histologic evaluation of the lesion demonstrated that treatment with didox and hydroxyurea significantly decreased lesion area and lumen loss. These results suggest that RR inhibition may be an effective new tool for the treatment of atheroproliferative disorders.

Document Type: Research Article

Affiliations: 1: Division of University Laboratory Animal Resources and the Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio, USA. gallaugher.8@osu.edu 2: Division of University Laboratory Animal Resources and the Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio 3: The Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida 4: Molecules for Health, Richmond, Virginia 5: The Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida;, Email: cardounel.1@ufl.edu

Publication date: December 1, 2009

More about this publication?
  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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