Stent Graft-Induced High Wall Stress Promoted Aortic Wall Failure and Aortic Wall Injurious Complications After TEVAR: A Study of Numerical Simulation and Bioinformatics Analysis Based on Pig Models.

Abstract

Objectives: Stent graft-related aortic injury is a major complication after thoracic endovascular aortic repair (TEVAR) and seriously affects patient prognosis. However, the distribution characteristics of aortic wall stress under the action of stent grafts and the mechanism of abnormal wall stress leading to aortic wall injury and adverse remodeling were unclear. The aim of this study was to explore the potential mechanisms of high wall stress on the structural and functional alterations of the aortic wall by combining animal experiments, numerical simulations, and bioinformatics.

Methods: We observed stent graft-induced aortic injury by performing fenestrated TEVAR in 6 pigs, and quantitatively analyzed and visualized the stress distribution of the aortic wall under the stent graft through numerical simulation. Hematoxylin and eosin (HE) staining, Masson's trichrome staining, Verhoeff's Van Gieson (EVG) staining, and immunostaining were used to evaluate pathological changes in the aorta. Based on the numerical simulation results, the corresponding high-stress and low-stress regions of the aortic wall were subjected to bulk-RNA sequencing, and hub genes were identified by bioinformatics analysis.

Results: Stent grafts were successfully implanted in 5 pigs. In all computational models, we found that obvious deformation and characteristic maximum stress concentration occurred on the side of the greater curve of the aortic arch in contact with the stent graft tip, and the high wall stress concentration areas were highly consistent with the obvious pathological injury area. Subsequent pathological analysis revealed that high wall stress-induced confusion and fragmentation of elastic fibers, collagen deposition, loss and phenotypic switching of vascular smooth muscle cells, and increased inflammatory responses. Gene expression profiles of the aortic wall under different wall stress conditions were described for the first time, and the hub genes (TGFB1, CDH5, DCN, ITGA5, ITGB3, and WT1) that may be involved in regulating the aortic injury and remodeling process in response to high wall stress stimulation were identified.

Conclusions: This study revealed a panoramic view of stent graft-associated high wall stress-induced aortic wall injury through technical approaches of multiple dimensions. Understanding these biomechanical features and hub genes is pivotal for advancing our comprehension of the complications associated with aortic injury after TEVAR and facilitating the development of future therapeutic interventions.

Clinical impact: This study revealed a panoramic view of stent graft-associated high wall stress-induced aortic wall injury through technical approaches of multiple dimensions. The biomechanical distribution characteristics of the aortic wall, the secondary pathological injury and the alteration of gene expression profile under the action of stent graft were comprehensively revealed by animal experiments for the first time. This will advance clinicians' comprehension of complications associated with aortic injury after TEVAR, provide a new biomechanical perspective for the rational preoperative planning of TEVAR and the management of postoperative complications, and facilitate the development of future therapeutic interventions and stent graft device designs.