Role of Leukocyte Elastase in Preventing Cellular Re-Colonization of the Mural Thrombus

Fontaine, Vincent; Touat, Ziad; Mtairag, El Mostafa; Vranckx, Roger; Louedec, Liliane; Houard, Xavier; Andréassian, B; Sebbag, Uriel; Palombi, Tonino; Jacob, Marie‐Paule; Meilhac, Olivier; Michel, Jean‐Baptiste

doi:10.1016/s0002-9440(10)63766-2

Cited by 124 publications

(156 citation statements)

References 70 publications

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“…To analyze the contribution of TWEAK on VSMC viability, we induce VSMC death with recombinant elastase. 26 As expected, elastase decreased VSMC viability in a dose-dependent manner (not shown). In addition, no effect on VSMC viability was observed after incubation with TWEAK alone.…”

Section: Tweak or Fn14 Deficiency Reduces Vascular Cells Apoptosissupporting

confidence: 77%

“…Elastase is one of the most potent proteases reported to be present in the pathological arterial wall and is able to induce apoptosis subsequent to extracellular matrix degradation. 26 We have observed that WT mice lost more VSMC than either TWEAK or Fn14-null mice. In vitro experiments showed that TWEAK alone did not decrease VSMC viability.…”

Section: Tweak/fn14 Deficiency Diminished Aortic Aneurysmmentioning

confidence: 80%

See 1 more Smart Citation

Tumor Necrosis Factor−Like Weak Inducer of Apoptosis or Fn14 Deficiency Reduce Elastase Perfusion−Induced Aortic Abdominal Aneurysm in Mice

2014

JAHA

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Section: Tweak or Fn14 Deficiency Reduces Vascular Cells Apoptosissupporting

confidence: 77%

Section: Tweak/fn14 Deficiency Diminished Aortic Aneurysmmentioning

confidence: 80%

Tumor Necrosis Factor−Like Weak Inducer of Apoptosis or Fn14 Deficiency Reduce Elastase Perfusion−Induced Aortic Abdominal Aneurysm in Mice

2014

JAHA

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“…2,3 However, recent evidence is revealing a previously unappreciated role of PMN in experimental 4,5 and human 6,7 AAAs. PMNs can contribute to main mechanisms of AAA evolution, namely intraluminal thrombus (ILT) formation, oxidative stress, proteolytic degradation of the aortic media, and adventitial inflammation.…”

mentioning

confidence: 99%

Proteomic Analysis of Polymorphonuclear Neutrophils Identifies Catalase as a Novel Biomarker of Abdominal Aortic Aneurysm: Potential Implication of Oxidative Stress in Abdominal Aortic Aneurysm Progression

Ramos-Mozo

Madrigal‐Matute

Martinez-Pinna

et al. 2011

ATVB

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Objective-Polymorphonuclear neutrophils (PMNs) play a main role in abdominal aortic aneurysm (AAA) progression.We have analyzed circulating PMNs isolated from AAA patients and controls by a proteomic approach to identify proteins potentially involved in AAA pathogenesis. Methods and Results-PMNs from 8 AAA patients (4 large AAA Ͼ5 cm and 4 small AAA 3-5 cm) and 4 controls were analyzed by 2D differential in-gel electrophoresis. Among differentially expressed spots, several proteins involved in redox balance were identified by mass spectrometry (eg, cyclophilin, thioredoxin reductase, catalase). Diminished catalase expression and activity were observed in PMNs from AAA patients compared with controls. In contrast, PMNs from AAA patients displayed higher H 2 O 2 and myeloperoxidase levels than PMNs from controls. Moreover, a significant decrease in catalase mRNA levels was observed in PMNs after phorbol 12-myristate 13-acetate incubation. Catalase plasma levels were also decreased in large (nϭ47) and small (nϭ56) AAA patients compared with controls (nϭ34). We observed catalase expression in AAA thrombus and thrombus-conditioned medium, associated with PMN infiltration. Furthermore, increased H 2 O 2 levels were observed in AAA thrombus-conditioned medium compared with the media layer. Key Words: aneurysms Ⅲ antioxidants Ⅲ leukocytes A bdominal aortic aneurysm (AAA) is an important health problem in elderly. In cross-sectional studies, the prevalence varies from 3% to 8%. 1 In elderly men, AAAs may cause as much as 2% to 3% of all deaths. 1 Because AAAs are usually asymptomatic, the present clinical challenges are early diagnosis and deciphering the biological mechanisms responsible for the progressive dilatation and final rupture to develop new diagnostic and therapeutic approaches. Conclusion-DiminishedAlthough polymorphonuclear neutrophils (PMNs) represent the major class of leukocytes, they have received little attention in atherothrombosis. 2,3 However, recent evidence is revealing a previously unappreciated role of PMN in experimental 4,5 and human 6,7 AAAs. PMNs can contribute to main mechanisms of AAA evolution, namely intraluminal thrombus (ILT) formation, oxidative stress, proteolytic degradation of the aortic media, and adventitial inflammation. 8 AAAs are characterized by the presence of a mural ILT-containing platelets, red blood cells (RBCs), and PMNs, particularly abundant within the luminal layer of human thrombus. 6 -8 AAAs are also characterized by destructive connective tissue remodeling, including depletion of aortic elastin and fragmentation of medial elastic fibers. 9 Finally, inflammatory cells (macrophages and neutrophils) are also evident within the adventitia of human AAAs. 10 Interestingly, PMNs depletion is able to inhibit experimental AAA formation. 11 More recently, short-term preoperative doxycycline therapy improved the proteolytic balance in human AAA, presumably via an effect on aortic wall neutrophil content. 12 These data highlight the potential interest of analyzing the PMNs p...

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“…We have previously demonstrated that neutrophil invasion and activation within the thrombus of human aortic abdominal aneurysms are the main biological impediments to the repair process that shifts the thrombus phenotype from a potential healing substrate to an aggressive neotissue. 15 One of the strengths of the study by Mangold et al 13 resides in the use of human biological material. When compared with mice, in which the blood count is low in granulocytes (<20%), polymorphonuclear neutrophils are the predominant type of circulating leukocytes (50%-70%) in humans and are therefore systematically present in human thrombi.…”

Section: Article See P 1182mentioning

confidence: 99%

Thrombi and Neutrophils

Michel

Ho‐Tin‐Noé

2015

Circulation Research

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Role of Leukocyte Elastase in Preventing Cellular Re-Colonization of the Mural Thrombus

Cited by 124 publications

References 70 publications

Tumor Necrosis Factor−Like Weak Inducer of Apoptosis or Fn14 Deficiency Reduce Elastase Perfusion−Induced Aortic Abdominal Aneurysm in Mice

Tumor Necrosis Factor−Like Weak Inducer of Apoptosis or Fn14 Deficiency Reduce Elastase Perfusion−Induced Aortic Abdominal Aneurysm in Mice

Proteomic Analysis of Polymorphonuclear Neutrophils Identifies Catalase as a Novel Biomarker of Abdominal Aortic Aneurysm: Potential Implication of Oxidative Stress in Abdominal Aortic Aneurysm Progression

Thrombi and Neutrophils

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