Submitted on June 10, 2005
Accepted on January 17, 2006
Linkage Analysis of Neointimal Hyperplasia and Vascular Wall Transformation Following Balloon Angioplasty
Andrea L Nestor1*, George T Cicila2, Seth E Karol1, Kay M Langenderfer1, Stacy L Hollopeter1, and David C Allison3
1 Department of Surgery, Medical University of Ohio, Toledo, OH, USA; Microscopy Imaging Center, Medical University of Ohio, Toledo, OH, USA
2 Department of Physiology, Pharmacology, Metabolism and Cardiovascular Science, Medical University of Ohio, Toledo, OH, USA
3 Department of Surgery, Medical University of Ohio, Toledo, OH, USA; Department of Physiology, Pharmacology, Metabolism and Cardiovascular Science, Medical University of Ohio, Toledo, OH, USA; Microscopy Imaging Center, Medical University of Ohio, Toledo, OH, USA
* To whom correspondence should be addressed. E-mail: anestor{at}meduohio.edu.
Neointimal hyperplasia (NIH), a result of vascular injury, is due to the migration and proliferation of smooth muscle cells through the media and internal elastic lamina leading to vascular occlusion. We utilized a rat model to find the genetic regions controlling NIH after endothelial denudation in two divergent inbred strains of rats. The BN and SHR rat strains have a 2.5 fold difference in injury-induced NIH. A population of 301 F2 (SHR X BN) rats underwent a standard vascular injury followed by phenotyping eight weeks post-injury to identify quantitative trait loci (QTL) responsible for this strain difference. Interval mapping identified two %NIH QTL on rat chromosomes 3 and 6 (LOD scores 2.5, 2.2) and QTL for other injured vascular wall changes on rat chromosomes 3, 4, and 15 (LOD scores 2.0 - 4.6). Also, QTL for control vessel media width (MW) and media area (MA) were found on chromosome 6 with LOD scores of 2.3 and 2.5, suggesting linkage exists between these control-vessel parameters and NIH production. These results represent the first genetic analysis for the identification of neointimal hyperplasia QTL and QTL associated with the vascular injury response.
