In an effort to characterize intimal hyperplastic lesions, we have undertaken a time-course study in a canine endarterectomy model of intimal hyperplasia. Twenty dogs underwent surgical endarterectomies of the carotid arteries. A total of 23 of 27 (85%) injured arteries were patent, which consisted of 6, 8, 5, and 4 arteries found to be patent at 1, 2, 5, and 11 weeks, respectively. Measurable intimal thickening developed at 1 week (0.08 ± 0.01 mm) and at 2 weeks (0.13 ± 0.02 mm), maximized at 5 weeks (0.29 ± 0.03 mm), and subsided at 11 weeks (0.21 ± 0.01 mm) after injury. Endothelial cells covering intimal hyperplastic tissues were seen only at 11 weeks. The intimal cell proliferation rate reached a maximum of 24% at 1 week, decreased dramatically at 2 weeks, and remained at low levels but higher than baseline levels at 5 and 11 weeks. Extracellular matrix (ECM) content accounted for 29% of total intimal volume at 1 week after endarterectomy and increased to 37, 40, and 47% at 2, 5, and 11 weeks, respectively. These data demonstrate that maximum intimal cell proliferation occurs at 1 week and maximum intimal hyperplasia at 5 weeks after arterial injury. Intimal ECM content increased with time after injury throughout the duration of this study. The uniform and consistent intimal lesion that was established in this large animal model is clinically relevant and can be used to study cellular and molecular mechanisms of restenosis and to evaluate therapeutic interventions.
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