Influence of intraluminal thrombus on structural and cellular composition of abdominal aortic aneurysm wall.
BACKGROUND
It has been suggested that the intraluminal thrombus of abdominal aortic aneurysm (AAA) affects the underlying vessel wall. Aneurysm enlargement has been associated with growth of thrombus, and rupture has been proposed to occur after bleeding into the thrombus. To examine how thrombus affects the vessel wall, we compared the morphology of aneurysm wall covered with thrombus with wall segments exposed to flowing blood. Material and methods Sixteen patients (14 men, 2 women; age range, 56-79 years) undergoing elective repair of AAA, where computed tomography scans showed thrombus and segments of the aneurysm wall exposed to flowing blood, were included in the study. Specimens from the aneurysm were taken for light and electron microscopy. Masson trichrome staining was performed for wall thickness determination and demonstration of collagen, and Weigert-van Gieson staining for elastin. The cellular composition was analyzed by immunohistochemistry with antibodies against CD3 for T cells, CD4 for T helper cells, CD8 for T cytotoxic cells, CD20 for B cells, CD68 for macrophages, and smooth muscle alpha-actin for smooth muscle cells (SMCs). Caspase-3 staining and TUNEL analysis were performed to evaluate apoptosis.


RESULTS
The aneurysm wall covered with thrombus was thinner and contained fewer elastin fibers, and the few that were found were often fragmented. This part of the wall also contained fewer SMCs and more apoptotic nuclei than the wall exposed to flowing blood. Clusters of inflammatory cells were detected in the media of the aneurysm wall and in higher numbers in the parts covered with thrombus. Electron microscopy showed that the aneurysm wall without thrombus contained a dense collagenous matrix with differentiated SMCs. In the segment covered with thrombus, SMCs were more dedifferentiated (synthetic) and apoptotic or necrotic. There were also an increased number of inflammatory cells located in close contact with SMCs in various stages of apoptosis.


CONCLUSIONS
The aneurysm wall covered with thrombus is thinner and shows more frequent signs of inflammation, apoptosis of SMCs, and degraded extracellular matrix. These findings suggest that thrombus formation and accumulation of inflammatory cells may perturb the structural integrity and stability of the vessel wall and thereby increase the risk for aneurysm rupture.
Kazi
Monsur
M
Division of Vascular Surgery, Karolinska Hospital and Institute, S-171 76 Stockholm, Sweden.
Thyberg
Johan
J
Religa
Piotr
P
Roy
Joy
J
Eriksson
Per
P
Hedin
Ulf
U
Swedenborg
Jesper
J
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000473:pathology*; D001019:Aortic Rupture / Q000209:etiology; D017209:Apoptosis / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000648:ultrastructure; D009336:Necrosis; D012039:Regional Blood Flow / Q000502:physiology; D012307:Risk Factors; D013927:Thrombosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*