Abstract
Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture and subsequent high mortality. Establishment of medical therapies for the prevention of AAAs requires further understanding of the molecular pathogenesis of this condition. This report details the possible involvement of Osteoprotegerin (OPG) in the prevention of AAAs through inhibition of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In CaCl2-induced AAA models, both internal and external diameters were significantly increased with destruction of elastic fibers in the media in Opg knockout (KO) mice, as compared to wild-type mice. Moreover, up-regulation of TRAIL expression was observed in the media by immunohistochemical analyses. Using a culture system, both the TRAIL-induced expression of matrix metalloproteinase-9 in smooth muscle cells (SMCs) and the chemoattractive effect of TRAIL on SMCs were inhibited by OPG. These data suggest that Opg may play a preventive role in the development of AAA through its antagonistic effect on Trail.
Highlights
An abdominal aortic aneurysm (AAA) is a progressive dilation of the aorta, which results in rupture with high mortality ratio
We found that dilation of the abdominal aorta was enhanced with complete destruction/disappearance of elastic fibers in the medial layer of Opg-KO mice by using a CaCl2-induced AAA model
Induction of Mmp-9 by Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) occurred via the Jun NH2-terminal kinase (JNK) pathway, and Timp-1 was induced via NF-kB and the JNK pathway
Summary
An abdominal aortic aneurysm (AAA) is a progressive dilation of the aorta, which results in rupture with high mortality ratio. The infiltration of macrophages and disruption of medial elastic fibers that occur in this condition are believed to be associated with inflammation [1]. Since inflammation is a common underlying feature of both AAAs and atherosclerosis, these two conditions are considered to be closely related [2]. It has not yet been determined, whether the relationship between AAAs and atherosclerosis is causal or if these conditions merely share common risk factors, such as smoking, hypertension, and obesity [3].
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