Expression and localization of tumour necrosis factor-α and its converting enzyme in human abdominal aortic aneurysm

Satoh, Hidetoshi; Nakamura, Motoyuki; Satoh, Mamoru; Nakajima, Takayuki; Izumoto, Hiroshi; Maesawa, Chihaya; Kawazoe, K; Masuda, Tomoyuki; Hiramori, Katsuhiko

doi:10.1042/cs20030189

Cited by 56 publications

(78 citation statements)

References 27 publications

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“…Loss of cellular density in the vessel wall decreases cell mass and structural support, facilitating ballooning and aneurysm formation. This occurs through various pathways mediated by proinflammatory and proapoptotic cytokines, such as TNF␣, interleukin-1, and IFN␥ (13,(36)(37)(38). However, apoptosis does not appear to be an important factor in development of coronary artery aneurysms in this model of KD.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease

Lau¹,

Duong²,

Itô³

et al. 2008

Arthritis & Rheumatism

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Objective. Kawasaki disease (KD) is a multisystem vasculitis leading to damage in the coronary circulation and aneurysm formation. Because cardiac tissue from affected children is not available, investigation of the mechanisms responsible for coronary artery damage in KD requires use of a disease model. The present study was undertaken to examine, in an experimental model, the role of matrix metalloproteinase 9 (MMP-9) on coronary artery inflammation and vascular damage.Methods. C57BL/6 mice were injected with Lactobacillus casei cell wall extract to induce coronary arteritis. Hearts were isolated and assayed for MMP-9 protein expression and enzymatic activity by immunoblotting or confocal microscopy and zymography, respectively. MMP-9-deficient mice were used to examine the necessity of MMP-9 for disease development.Results. Localized inflammation at the coronary artery led to elastin breakdown and aneurysm formation. This occurred in the absence of smooth muscle cell apoptosis. Following disease induction, there was an increase in the amount and enzymatic activity of MMP-9, an elastolytic protease. MMP-9 was upregulated by tumor necrosis factor ␣ (TNF␣) and produced primarily by vascular smooth muscle cells. In MMP-9-deficient animals, vascular inflammation continued to develop, but the incidence of elastin breakdown was significantly reduced. Elastin breakdown in the coronary artery was virtually eliminated by ablation of MMP-9.Conclusion. These findings show that TNF␣ upregulates expression of MMP-9, an important proteinase responsible for extracellular matrix breakdown, leading to coronary artery damage in this model of KD. These results have important implications regarding treatments for improving coronary outcome in affected children.

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Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease

Lau¹,

Duong²,

Itô³

et al. 2008

Arthritis & Rheumatism

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“…This could be explained by the fact that our surgeons take tissue specimens from AAAs from the mid-portion of the AAA, although more TNF-␣ mRNA and TNF-␣-converting enzyme (TACE) mRNA had been described in the transition zone of AAAs. 39 Thus the mid-portion of AAAs reflects more a non-or postinflammatory status, whereas a more active inflammatory status would be expected in the transition zone of AAAs. The source of biopsies could thus explain the lack of T cells in some of our specimens taken from the midportion of the AAAs.…”

Section: The Correlation Between Cd28mentioning

confidence: 99%

High Prevalence of Circulating CD4⁺CD28⁻T-Cells in Patients With Small Abdominal Aortic Aneurysms

Duftner

Seiler²,

Klein-Weigel³

et al. 2005

ATVB

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Objective-To assess the possible role of proinflammatory CD28Ϫ T cells in abdominal aortic aneurysms (AAAs). Animal studies and human tissue studies suggest a role for interferon (IFN)-␥-producing T cells in the development and progression of AAAs. Methods and Results-Fluorescence-activated cells sorter analysis of peripheral blood samples and measurement of AAA size using sonography were performed in 101 AAA patients and 38 healthy controls. Key Words: aortic disease Ⅲ aneurysms Ⅲ leukocytes Ⅲ immune system Ⅲ human A bdominal aortic aneurysm (AAA) is a common disease with a prevalence of 3% of individuals aged 60 years and older and is a potentially lethal disorder causing Ϸ15 000 deaths annually in the United States. 1 Recent human tissue studies and animal models have led now to a paradigm shift in the pathogenetic concept of AAAs. Rather than a simple degenerative process, the majority of AAAs has proven to be a complex and dynamic remodeling process. In brief, studies of human AAA tissues have identified extensive inflammatory infiltrates in both the media and the adventitia, 2 leading to an increased expression of proinflammatory cytokines and C-reactive protein (CRP) in aneurysmal tissue. [3][4][5] The presence of vascular-associated lymphoid tissue (VALT) with lymphoid follicles and lymph node-like structures in the adventitia of AAAs suggests a role for immunocompetent and antigen presenting cells not only in atherosclerosis 6 but also in AAA disease. 2 The role for T cells has been further supported by immunogenetic findings with associations between AAA and human leukocyte antigen class II molecules. 7 Infiltration of the adventitia usually occurs together with medial thinning. This inflammatory process triggers the production of metalloproteinases and apoptosis of medial smooth muscle cells thus explaining the disruption of the orderly lamellar structure in aortic aneurysms.Recently, a subgroup of proinflammatory T cells has been identified in patients with immune-mediated disorders including rheumatoid arthritis, 8 -9 ankylosing spondylitis, 10 multiple sclerosis, 11 Wegener granulomatosis, 12 and unstable angina, 13 which lack the costimulatory molecule CD28 on their surface and are considered as markers for chronic inflammation and early aging. 14 Under these circumstances the CD28 Ϫ T cells are part of the CD4 ϩ as well as the CD8 ϩ T cell compartment, persist over years, and include most of the oligoclonally expanded T cells. Phenotypically, CD4 ϩ CD28 Ϫ T cells from rheumatoid arthritis and ankylosing spondylitis patients and CD8 ϩ CD28 Ϫ T cells from aged persons, rheumatoid arthritis, and melanoma patients share the expression of various natural killer (NK) cell receptors and lack the expression of the lymphocyte marker CD7. 9,15-16 Functionally these T cells are capable to release large amounts of interferon (IFN)-␥, perforin, and granzyme B, providing them with the possibility to lyse target cells. 17 In the pathogenesis of coronary arteriosclerosis, the critical role of IFN-␥ was alread...

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“…Interestingly, expression of both TNF-a and its activating enzyme TACE are not only higher in AAAs compared to control aortas, they are also higher in the neck compared with the apex of the lesion, where they colocalize with macrophages of the media and adventitia. TNF-a can also induce other inflammatory cytokines and several MMPs, promote apoptosis, and increase uPA, tPA, and PAI-1 levels (which are pro-angiogenic) [107]. The delivery of a TNF-a specific binding protein has even been shown to prevent AAA formation in a rat elastase perfusion model [107].…”

Section: Implications Of Spatial Distribution-the Shoulder and Neck Rmentioning

confidence: 99%

“…TNF-a can also induce other inflammatory cytokines and several MMPs, promote apoptosis, and increase uPA, tPA, and PAI-1 levels (which are pro-angiogenic) [107]. The delivery of a TNF-a specific binding protein has even been shown to prevent AAA formation in a rat elastase perfusion model [107].…”

Section: Implications Of Spatial Distribution-the Shoulder and Neck Rmentioning

confidence: 99%

Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

Wilson

Virag

Achille

et al. 2013

Journal of Biomechanical Engineering

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Most computational models of abdominal aortic aneurysms address either the hemodynamics within the lesion or the mechanics of the wall. More recently, however, some models have appropriately begun to account for the evolving mechanics of the wall in response to the changing hemodynamic loads. Collectively, this large body of work has provided tremendous insight into this life-threatening condition and has provided important guidance for current research. Nevertheless, there has yet to be a comprehensive model that addresses the mechanobiology, biochemistry, and biomechanics of thrombus-laden abdominal aortic aneurysms. That is, there is a pressing need to include effects of the hemodynamics on both the development of the nearly ubiquitous intraluminal thrombus and the evolving mechanics of the wall, which depends in part on biochemical effects of the adjacent thrombus. Indeed, there is increasing evidence that intraluminal thrombus in abdominal aortic aneurysms is biologically active and should not be treated as homogeneous inert material. In this review paper, we bring together diverse findings from the literature to encourage next generation models that account for the biochemomechanics of growth and remodeling in patient-specific, thrombus-laden abdominal aortic aneurysms.

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Expression and localization of tumour necrosis factor-α and its converting enzyme in human abdominal aortic aneurysm

Cited by 56 publications

References 27 publications

Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease

Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease

High Prevalence of Circulating CD4⁺CD28⁻T-Cells in Patients With Small Abdominal Aortic Aneurysms

Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

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Expression and localization of tumour necrosis factor-α and its converting enzyme in human abdominal aortic aneurysm

Cited by 56 publications

References 27 publications

Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease

Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease

High Prevalence of Circulating CD4+CD28−T-Cells in Patients With Small Abdominal Aortic Aneurysms

Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

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High Prevalence of Circulating CD4⁺CD28⁻T-Cells in Patients With Small Abdominal Aortic Aneurysms