TY - JOUR
T1 - Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue
AU - Behr-Rasmussen, Carsten
AU - Lindholt, Jes S
AU - Urbonavicius, Sigitas
AU - Halekoh, Ulrich
AU - Jensen, Pia Søndergaard
AU - Stubbe, Jane
AU - Rasmussen, Lars Melholt
AU - Beck, Hans Christian
N1 - © 2018 American Heart Association, Inc.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
KW - arteries
KW - extracellular matrix proteins
KW - myocardial infarction
KW - porosity
KW - proteome
U2 - 10.1161/ATVBAHA.117.310126
DO - 10.1161/ATVBAHA.117.310126
M3 - Journal article
C2 - 30002058
SN - 1079-5642
VL - 38
SP - 2254
EP - 2267
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 9
ER -