Fluid upstream shear stress of rabbit aortic stenosis inhibits neointimal hyperplasia by promoting endothelization after balloon injury

Abstract

Background: Atherosclerosis is associated with disturbed blood flow characterized by low and oscillatory shear stress (SS), however, few study directly links SS to neointimal hyperplasia in animal model. This study was focused on the effects of changed SS upon the neointimal hyperplasia which responded to balloon injury in a novel rabbit model with partially-constricted abdominal aorta. Methods: We established a rabbit model subjected to partial abdominal aortic constriction with a cylinder-shaped cannula as a model of disturbed flow, which was similar to the hemodynamic features of stenosis caused by atherosclerosis plaque. Further, balloon injury was performed to investigate the relationship between SS and neointimal hyperplasia. Four weeks later, the abdominal aorta was assessed with digital subtraction angiography (DSA) and intravascular ultrasound (IVUS). The vascular sections were embedded in paraffin blocks for morphometric analysis to evaluate neointimal hyperplasia, and anti-CD31 immunohistochemical staining was for endothelialization ratio. Results: In upstream the stenosis, the changed SS leads to neointimal hyperplasia compared with normal SS (11,729 ± 1205 vs 8418 ± 737, P = 0.023). However, the upstream SS of the stenosis can promote vascular re-endothelialization after balloon injury compared with normal SS, verified by endothelialization ratio (0.36 ± 0.03 vs 0.32 ± 0.03, P = 0.017), thereby attenuate neointimal hyperplasia (64,851 ± 3995 vs 68,335 ± 3867, P = 0.018). Conclusion: The upstream SS of stenosis, not downstream SS, inhibits the neointimal hyperplasia after balloon injury by promoting vascular re-endothelializtion.