Distinction in genetic determinants for injury-induced neointimal hyperplasia and diet-induced atherosclerosis in inbred mice.
Five inbred strains of mice differing in susceptibility to diet-induced atherosclerosis were compared for neointimal hyperplasia after endothelial denudation with an epoxy resin-modified catheter probe. Results showed that all animals responded similarly to the arterial injury, with increased medial area and thickness after 14 days. In contrast, a significant strain-specific difference in neointimal formation after injury was observed. The atherosclerosis-susceptible C57L/J mice were also susceptible to injury-induced neointimal hyperplasia, and the C3H mice were resistant to both forms of vascular diseases. The 129/Sv mice, which displayed an intermediate level of diet-induced atherosclerosis, also displayed an intermediate level of injury-induced neointimal hyperplasia. Interestingly, the atherosclerosis-susceptible C57BL/6 mice were resistant to neointimal hyperplasia after endothelial denudation, whereas the atherosclerosis-resistant FVB/N mice were susceptible, displaying massive neointimal hyperplasia after arterial injury. All (C57L/JxC57BL/6)F1 hybrid mice were resistant to injury-induced neointimal hyperplasia. Moreover, N2 mice generated from backcrossing the F1 hybrid mice to the susceptible C57L/J mice displayed a range of arterial response to injury, spanning the most severe to the most resistant phenotype. These results indicate that injury-induced neointimal hyperplasia and diet-induced atherosclerosis are controlled by distinct sets of genes; the former appeared to be determined by recessive genes at > or =2 loci.
Kuhel
David G
DG
Center of Lipid and Arteriosclerosis Studies, Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0529, USA.
Zhu
Binghua
B
Witte
David P
DP
Hui
David Y
DY
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D002339:Carotid Arteries / Q000473:pathology / Q000601:surgery; D003433:Crosses, Genetic; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006965:Hyperplasia; D007113:Immunity, Innate / Q000235:genetics; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000601:surgery; D017539:Tunica Intima / Q000473:pathology*
D008055:Lipids; D008074:Lipoproteins