Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Abstract

Objective-Porosity of the intraluminal thrombus (ILT) is believed to convey biologically active components from the bloodstream toward the aneurismal wall. Accumulation of molecules in the abdominal aortic aneurysmatic tissue may influence vascular protein turnover and regulate abdominal aortic aneurysm growth. We sought to identify proteins with concentrations in the ILT and the abdominal aortic aneurysm wall which associate with aneurysmal expansion rate. Approach and Results-Proteomic analysis by liquid chromatography tandem-mass spectrometry of separated wall and ILT samples was correlated with preoperative aneurysmal growth rate in 24 individuals operated electively for infrarenal abdominal aortic aneurysm. The median preoperative growth rate was 3.8 mm/y (interquartile range, 3) and the mean observational time was 3.3±1.7 years. Plasma components dominated the group of proteins with tissue concentrations, which correlate positively with growth rates (P<0.001, Fisher exact test, both in the ILT and the wall). In contrast, in the wall and thrombus samples, ECM (extracellular matrix) proteins were significantly more prevalent in the group of proteins with negative correlations to growth rates (P<0.05, Fisher exact test). Similarly, a long series of proteins, related to cellular functions correlated negatively to growth rates. Conclusions-When the preoperative aneurysmatic growth rate has been high, the concentration of many plasma proteins residing in the ILT and the aneurysmatic tissue is also high, compatible with the hypothesis of increased tissue porosity and accumulation of plasma components as a driver of aneurysm expansion. Moreover, many matrix and cellular proteins which are found in high concentrations in slower-growing aneurysms provides new knowledge about potential treatment targets. Visual Overview-An online visual overview is available for this article.

Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation

“…Arresten and Canstatin (degradation products of COL4A1 and -A2, respectively) have anti-angiogenic activity 7 , but whether these peptides play a significant role in AAA pathogenesis remains elusive. Recently, AXT107—a peptide derived from sequences of both COL4A1 and COL4A5 58 was proposed as a drug displaying strong anti-permeability effects on several vessel types 58 , 59 —an effect which could also be relevant in the context of AAA 60 .…”

Role of vascular remodeling in atherosclerosis and aortic aneurysm

“…137 Correspondingly, proteomic analysis showed that TRX protein in the human AAA wall sample is negatively correlates with the growth rate, which is in line with hypothesis that upregulation of TRX in defense against ROS may slow down the aneurysm expansion rate. 138 A similar dependency of TAA on increased ROS has been observed, as in vitro and ex vivo studies on human TAA tissue revealed that oxidative stress mediates VSMC phenotypic switching towards synthetic phenotype through connective tissue growth factor. 139 These results was further validated in a mouse model of TAA which showed similar pathology as observed in human tissue.…”

Association of Aneurysm Tissue Neutrophil Mediator Levels with Intraluminal Thrombus Thickness in Patients with Abdominal Aortic Aneurysm

“…It should be mentioned that the mediators from plasma and those produced by ILT-trapped neutrophils were observed both in the thrombus and in adjacent aneurysm walls. Additionally, one study has shown that canaliculi, through which cells and proteins travel, are also present in abluminal layers of ILT and the AAA walls and are even larger than those in luminal layers, which could allow both larger molecules and cells to reach the wall [ 53 , 54 ]. The presence of such a leaky ILT and a spongy vessel wall that can allow proteases and other unfavourable molecules to accumulate and degrade components of the wall could ultimately lead to AAA diameter widening and subsequent rupture.…”