Key result
Endograft implantation in porcine aortas acutely induced a significant stiffness gradient and increased expression of inflammatory cytokines and matrix metalloproteinases under pulsatile pressure.
Why the study?
Chronic aortic neck dilatation after EVAR weakens the structural seal and compromises long-term results, but the underlying mechanisms remain unclear.
Does endograft implantation induce vascular stiffness gradients and inflammatory remodeling in porcine abdominal aortas?
Does endograft implantation induce vascular stiffness gradients and inflammatory remodeling in porcine abdominal aortas?
Endograft-induced aortic stiffness gradients trigger early inflammatory remodeling processes under pulsatile pressure, providing a potential mechanism for late aortic neck dilatation.
Ex vivo model may clarify AND mechanisms after EVAR; leaves open clinical translation and preventive strategies.
Purpose: Endovascular aortic repair (EVAR) is the method of choice for most abdominal aortic aneurysm (AAA) patients requiring intervention. However, chronic aortic neck dilatation (AND) following EVAR progressively weakens the structural seal between vessel and endograft and compromises long-term results of the therapy. This experimental ex vivo study seeks to investigate mechanisms of AND. Materials and Methods: Porcine abdominal aortas (n=20) were harvested from slaughterhouse pigs and connected to a mock circulation. A commercially available endograft was implanted (n=10) or aortas were left untreated as controls (n=10). Vascular circumferential strain was assessed via ultrasound in defined aortic segments as a parameter of aortic stiffness. Histology and aortic gene expression analysis were performed to investigate potential changes of aortic wall structure and molecular differences due to endograft implantation. Results: We found that endograft implantation acutely induces a significant stiffness gradient directly at the interface between stented and unstented aortic segments under pulsatile pressure. Comparing stented aortas with unstented controls, we detected increased aortic expression levels of inflammatory cytokines ( Il6 and Ccl2 ) and matrix metalloproteinases ( Mmp2 and Mmp9 ) after 6 hours of pulsatile pressurization. This effect, however, was abolished when repeating the same experiment under 6 hours of static pressure. Conclusions: We identified endograft-induced aortic stiffness gradients as an early trigger of inflammatory aortic remodeling processes that might promote AND. These results highlight the importance of adequate endograft designs to minimize vascular stiffness gradients and forestall late complications, such as AND. Clinical Impact AND may compromise the long-term results following endovascular aortic repair. However, the mechanisms behind the underlying detrimental aortic remodeling are still unclear. In this study we find that endograft-induced aortic stiffness gradients induce an inflammatory aortic remodeling response consistent with AND. This novel pathomechanistic insight may guide the design of new aortic endografts that minimize vascular stiffness gradients and forestall late complications such as AND.
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Schellinger et al. (2023) studied abdominal aortic aneurysm (n=20). Endograft implantation vs. Untreated aortas was evaluated on Vascular circumferential strain and aortic gene expression. Endograft implantation in porcine aortas acutely induced a significant stiffness gradient and increased expression of inflammatory cytokines and matrix metalloproteinases under pulsatile pressure.
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