Abstract

Endovascular repair (EVAR) has become the standard procedure in treating thoracic (TAA) or abdominal aortic aneurysms (AAA). Not entirely free of complications, a persisting perfusion of the aneurysm after EVAR, called Endoleak (EL), leads to reintervention and risk of secondary rupture. How the aortic wall responds to the implantation of a stentgraft and EL is mostly uncertain. We present a pilot study to identify peptide signatures and gain new insights in pathophysiological alterations of the aortic wall after EVAR using matrix-assisted laser desorption or ionization mass spectrometry imaging (MALDI-MSI). In course of or accompanying an open aortic repair, tissue sections from 15 patients (TAA = 5, AAA = 5, EVAR = 5) were collected. Regions of interest (tunica media and tunica adventitia) were defined and univariate (receiver operating characteristic analysis) statistical analysis for subgroup comparison was used. This proof-of-concept study demonstrates that MALDI-MSI is feasible to identify discriminatory peptide signatures separating TAA, AAA and EVAR. Decreased intensity distributions for actin, tropomyosin, and troponin after EVAR suggest impaired contractility in vascular smooth muscle cells. Furthermore, inability to provide energy caused by impaired respiratory chain function and continuous degradation of extracellular matrix components (collagen) might support aortic wall destabilization. In case of EL after EVAR, this mechanism may result in a weakened aortic wall with lacking ability to react on reinstating pulsatile blood flow.

Highlights

  • Defined as a dilatation of the aortic wall by 1.5 times of the physiological diameter, aortic aneurysm is a common disease with an age-dependent prevalence of 8% and is a leading cause of death in men >65 years old

  • As the formation of an aortic aneurysm is largely caused by changes within the tunica media, we focus our interpretation of the results only on the peptide alterations observed in this area

  • A decrease in extracellular matrix or cytoskeletal proteins and electron carrier protein could be observed in aortic wall specimens after Endovascular repair (EVAR)

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Summary

Introduction

Defined as a dilatation of the aortic wall by 1.5 times of the physiological diameter, aortic aneurysm is a common disease with an age-dependent prevalence of 8% and is a leading cause of death in men >65 years old. Aortic aneurysms are characterized by inflammation, VSMC apoptosis, extracellular matrix (ECM) degradation and oxidative stress [3,4] This results in a weakened and instable aortic wall which is no longer able to withstand luminal blood pressure. The underlying pathophysiological changes in the aortic wall leading to EL and rupture after EVAR are unclear. Referring to aortic diseases, Mohamed et al emphasized the potential of the MALDI technique in a proof-of-concept study to provide useful information for underlying pathogenesis in aneurysms of the thoracic ascending aorta [26]. Alterations in proteomic signatures after EVAR might be used to gain insights into the underlying pathophysiological remodeling leading to complications such as EL or aortic rupture

Patient and Sample Cohort
MALDI-MSI
Protein Identification by Electrospray Ionization Tandem Mass Spectrometry
MALDI-MSI Data Processing for Statistical Analyses
Statistical Data Analysis
Clinical Characterization
MALDI-MSI Data
Summary
Impaired Vascular Smooth Muscle Cell Contractility after EVAR
Increased ECM Degradation after EVAR
Alteration of the Energy Supply after EVAR
Conclusions
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