Features of Autoimmunity in the Abdominal Aortic Aneurysm

Gregory, Anita K; Yin, N X; Capella, Joseph F.; Xia, Shichao; Newman, K M; Tilson, M. David

doi:10.1001/archsurg.1996.01430130087017

Cited by 104 publications

(85 citation statements)

References 9 publications

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“…Early studies focused on prevalence and natural history, attempting to define risk profiles for developing aneurysms and to determine whether additional factors might precipitate rupture. 1,3,14,15 The association of some aneurysms with connective tissue disorders led to genetic evaluations of families with multiple members affected and to the search for culprit genes. 1,2,16,17 Experiments have sought to identify enzymes in the aorta that might break down collagen and elastin, which compose major structural elements of the vessel wall.…”

Section: Discussionmentioning

confidence: 99%

Death of Smooth Muscle Cells and Expression of Mediators of Apoptosis by T Lymphocytes in Human Abdominal Aortic Aneurysms

et al. 1999

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Background-Thinning of the tunica media and rarefaction of smooth muscle cells (SMCs) characterize aneurysmal aortas. Apoptosis determines the cellularity and morphogenesis of tissue. Macrophages and T lymphocytes infiltrate the wall of abdominal aortic aneurysms (AAAs) and produce death-promoting proteins (perforin, Fas, and FasL). This study investigated whether apoptosis occurs in association with the expression of these proteins. Methods and Results-We examined signs of apoptosis and expression of death-promoting mediators in segments of AAAs from patients undergoing elective repair (nϭ20). Anti-␣-actin immunostaining showed a reduced number of SMCs in AAAs. In situ terminal transferase-mediated dUTP nick end-labeling (TUNEL) showed higher levels of DNA fragmentation in AAAs than in controls (nϭ5). The AAA walls contained more cells bearing markers of apoptosis than normal aorta (PϽ0.05, Student's t test). Double immunostaining identified SMCs and macrophages as the principal cell types displaying fragmented DNA. Immunohistochemistry revealed that AAAs but not normal aorta contained CD4

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Section: Discussionmentioning

confidence: 99%

Death of Smooth Muscle Cells and Expression of Mediators of Apoptosis by T Lymphocytes in Human Abdominal Aortic Aneurysms

et al. 1999

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“…Earlier concepts of aneurysm expansion envisaged a simple degenerative process but immunohistochemical, cellular, and molecular biological studies of human tissues and animal models of AAA have consistently shown large numbers of inflammatory cells, elevated levels of cytokines and matrix metalloproteinases (MMPs), and destruction of the elastic media (1,2). Although many aspects of AAA development are undefined, these observations have led to a paradigm shift in which AAA is seen as a complex remodeling rather than a simple degeneration process.…”

mentioning

confidence: 99%

Key Roles of CD4+ T Cells and IFN-γ in the Development of Abdominal Aortic Aneurysms in a Murine Model

Xiong

Zhao

Prall

et al. 2004

The Journal of Immunology

187

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Abdominal aortic aneurysm (AAA) is one of a number of diseases associated with a prominent inflammatory cell infiltrate and local destruction of structural matrix macromolecules. This inflammatory infiltrate is predominately composed of T lymphocytes and macrophages. Delineating specific contribution of these inflammatory cells and their cytokines in AAA formation is the key to understanding AAA and other chronic inflammatory disease processes. Our previous studies have demonstrated that macrophages are the major source of matrix metalloproteinase-9, which is required for aneurysmal degeneration in the murine AAA model. However, the role of CD4+ T cells, the most abundant infiltrates in aneurysmal aortic tissue, is uncertain. In the present study, we found that in the absence of CD4+ T cells, mice are resistant to aneurysm induction. Previous studies have shown that IFN-γ levels are increased in AAA. IFN-γ is a main product of T cells. Intraperitoneal IFN-γ was able to partially reconstitute aneurysms in CD4−/− mice. Furthermore, mice with a targeted deletion of IFN-γ have attenuation of MMP expression and inhibition of aneurysm development. Aneurysms in IFN-γ−/− mice can be reconstituted by reinfusion of competent splenocytes from the corresponding wild-type mice. This study demonstrates the pivotal role that T cells and the T cell cytokine, IFN-γ, play in orchestrating matrix remodeling in AAA. This study has important implications for other degenerative diseases associated with matrix destruction.

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“…Western immunoblotting techniques revealed the presence of multiple C3 degradation products in AAA. Increases in IgG1, 2, and 3 may be responsible for activation of complement in AAA by the classical pathway (Capella et al, 1996). Consistent with this finding, Stella et al (Stella et al, 1991) demonstrated that the interstitial matrix contained deposits of IgG, IgM and C3c together with an increase in type III collagen and a reduction in elastin which appeared fragmented and swollen.…”

Section: Immunoglobins and C3 Deposition In Aneurysmsmentioning

confidence: 76%

“…These findings suggest that these IgGs may participate in the development and progression of AAA because these IgGs binding to the matrix fibers in artery may initiate local classical pathway activation and mediate complement attack on the artery wall, leading to initiation of the formation of artery aneurysms associated with autoimmune disease. This prediction was further confirmed by increased C3 deposition, along with IgG content in the AAA (Capella et al, 1996). In 1996, Capella et al further demonstrated that compared to the amounts of IgG by subclass in normal aorta, AAA had increases of 193-fold in IgG1, 160-fold in IgG2, 389-fold in IgG3, and 627-fold in IgG4.…”

Section: Immunoglobins and C3 Deposition In Aneurysmsmentioning

confidence: 89%

“…Gregory et al used immunoblotting techniques to compare the reactivity of IgG (detected with secondary goat antihuman antibody) from fourteen patients with abdominal aortic aneurysm (AAA) with soluble proteins extracted from normal and aneurysmal aortas (Gregory et al, 1996). Immunoglobulins G purified from extracts obtained from nine patients with no AAA were used for control experiments.…”

Section: Immunoglobins and C3 Deposition In Aneurysmsmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Complement in the Pathogenesis of Artery Aneurysms

Liu¹,

Qin²,

Zhang³

et al. 2011

Etiology, Pathogenesis and Pathophysiology of Aortic Aneurysms and Aneurysm Rupture

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Features of Autoimmunity in the Abdominal Aortic Aneurysm

Abstract: Our findings suggest that there are autoimmune features of AAA disease that might not only be informative in terms of AAA origin but also lead to more precise forms of pharmacologic down-regulation of disease progression.

Cited by 104 publications

References 9 publications

Death of Smooth Muscle Cells and Expression of Mediators of Apoptosis by T Lymphocytes in Human Abdominal Aortic Aneurysms

Death of Smooth Muscle Cells and Expression of Mediators of Apoptosis by T Lymphocytes in Human Abdominal Aortic Aneurysms

Key Roles of CD4+ T Cells and IFN-γ in the Development of Abdominal Aortic Aneurysms in a Murine Model

The Role of Complement in the Pathogenesis of Artery Aneurysms

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