The Intraluminal Thrombus as a Source of Proteolytic Activity

Abstract

Most abdominal aortic aneurysms (AAAs) with a diameter indicating need for surgical repair contain intraluminal thrombus (ILT). The development of AAA is linked to degradation of elastin and collagen. These changes are more pronounced in the aneurysm wall covered by the ILT, which also shows more signs of inflammation and is thinner compared to the aneurysm wall exposed to flowing blood. The rate of increase in diameter of AAA correlates with increased thrombus growth and rupture. CT examinations of patients with rupture have demonstrated contrast appearing in the thrombus suggesting bleeding into it. Studies using gene array of human aneurysm specimens have shown that most matrix metalloproteinases (MMP) were upregulated in the thrombus-free wall. Analyses by zymography, however, demonstrate gelatinase activity in the interface between the thrombus and the underlying wall and in the media of the wall not covered by a thrombus. The thrombus contains large amounts of neutrophils. Neutrophil gelatinase associated lipocalin (NGAL) is involved in the regulation of MMP-9 activity and prevents its inactivation, thus augmenting the proteolytic effect. It has been identified in all layers of the ILT. The presence of NGAL/MMP-9 complexes throughout the thrombus and in the thrombus-covered wall may contribute to the increased proteolytic degradation seen in this wall segment. In conclusion, the presence, growth, and thickness of the ILT have been shown to be associated with growth and risk of rupture. The wall underlying the thrombus is thinner and shows more signs of proteolytic degradation. Increased proteolytic activity by MMP-9 may be mediated by binding to NGAL.