title: Linkage analysis of neointimal hyperplasia and vascular wall transformation after balloon angioplasty.
abstract: 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 used a rat model to find the genetic regions controlling NIH after endothelial denudation in two divergent inbred strains of rats. The Brown Norway (BN) and spontaneously hypertensive rat (SHR) 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 8 wk after injury to identify quantitative trait loci (QTL) responsible for this strain difference. Interval mapping identified two %NIH QTL on rat chromosomes 3 and 6 [logarithm of odds (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 that linkage exists between these control vessel parameters and NIH production. These results represent the first genetic analysis for the identification of NIH QTL and QTL associated with the vascular injury response.
authors.affiliation: Department of Surgery, Medical University of Ohio, Toledo, Ohio 43614-5804, USA. anestor@meduohio.edu
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Nestor
authors.forename: George T
authors.initials: GT
authors.lastname: Cicila
authors.forename: Seth E
authors.initials: SE
authors.lastname: Karol
authors.forename: Kay M
authors.initials: KM
authors.lastname: Langenderfer
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Hollopeter
authors.forename: David C
authors.initials: DC
authors.lastname: Allison
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D008040:Genetic Linkage; D006965:Hyperplasia / Q000235:genetics*; D007083:Iliac Artery / Q000473:pathology / Q000601:surgery; D008297:Male; D023421:Models, Animal; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D013045:Species Specificity; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*