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.
Highlights
Atherosclerosis is associated with disturbed blood flow characterized by low and oscillatory shear stress (SS), few study directly links SS to neointimal hyperplasia in animal model
There was no significant difference in body weight between the five groups, suggesting model was successfully established
The upstream SS of stenosis attenuates the lumen loss after balloon injury Four weeks later, the upstream and downstream vascular diameters of the separated arteries were measured by intravascular ultrasound (IVUS) in order to evaluate the vascular remodeling which was secondary to the balloon injury and/or constriction
Summary
Atherosclerosis is associated with disturbed blood flow characterized by low and oscillatory shear stress (SS), few study directly links SS to neointimal hyperplasia in animal model. A variety of models in vitro have been established to regulate shear flow to ECs, which are aimed to mimic important features of ECs flow environments in vivo. These models helped researchers to explore detailed mechanisms of their responses to SS, including the effects on EC morphology, cytoskeletal organization, proliferation, migration, permeability and junctional proteins, EC signaling and gene expression [1, 4, 5]
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