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

Abstract

BackgroundAtherosclerosis 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.MethodsWe 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.ResultsIn 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).ConclusionThe upstream SS of stenosis, not downstream SS, inhibits the neointimal hyperplasia after balloon injury by promoting vascular re-endothelializtion.

Pharmacological basis and new insights of resveratrol action in the cardiovascular system

“…Resveratrol restrains vascular SMC overgrowth and enhances re‐endothelialization, thus greatly reducing the risk of thrombosis (Yurdagul et al, ). This is consisitent with another study showing that upstream shear stress is important for facilitating re‐endothelialization to avoid neointimal hyperplasia (Liu et al, ). Further studies may focus on the synergistic effect of resveratrol and laminar shear stress in resisting age‐related cardiovascular events.…”

High shear stress attenuated arterial neointimal hyperplasia accompanied by changes in yes-associated protein/jun N-terminal kinase/vascular cell adhesion protein 1 expression

“…Finally, a significant NIH developed at the angioplasty site. In the study by Liu et al, 20 an arterial stenosis occurred upstream rather than downstream of the angioplasty site. At the same time, blood flow and shear stress decreased.…”

“…19 Spiguel et al 6 found that low shear stress could enhance NIH caused by balloon injury. However, Liu et al 20 found that the combination of low SS and balloon injury did not result in more significant NIH than balloon injury alone. In the study by Spiguel et al, 6 arterial stenosis occurred downstream of the angioplasty site.…”