Aortic aneurysms secrete interleukin-6 into the circulation

Dawson, Joe; Cockerill, Gillian; Choke, Edward; Am, Belli; Loftus, Ian; Thompson, Matt

doi:10.1016/j.jvs.2006.09.049

Cited by 110 publications

(104 citation statements)

References 40 publications

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“…1a-e). Mechanistically, increased expression of matrix metalloprotease-9 (MMP9, as a marker of vascular remodelling) 23 , F4/80 (as a marker of macrophages) 24,25 and IL-6 (as a marker of inflammation) 16,[26][27][28][29][30] were seen in the aorta (Fig. 1f).…”

Section: Resultsmentioning

confidence: 99%

Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma

et al. 2015

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Aortic dissection and intramural haematoma comprise an aortopathy involving separation of the aortic wall. Underlying mechanisms of the condition remain unclear. Here we show that granulocyte macrophage colony-stimulating factor (GM-CSF) is a triggering molecule for this condition. Transcription factor Krüppel-like factor 6 (KLF6)-myeloid-specific conditional deficient mice exhibit this aortic phenotype when subjected to aortic inflammation. Mechanistically, KLF6 downregulates expression and secretion of GM-CSF. Administration of neutralizing antibody against GM-CSF prevents the condition in these mice. Conversely, administration of GM-CSF in combination with aortic inflammation to wild-type mice is sufficient to induce the phenotype, suggesting the general nature of effects. Moreover, patients with this condition show highly increased circulating levels of GM-CSF, which is also locally expressed in the dissected aorta. GM-CSF is therefore a key regulatory molecule causative of this aortopathy, and modulation of this cytokine might be an exploitable treatment strategy for the condition.

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Section: Resultsmentioning

confidence: 99%

Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma

et al. 2015

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“…Of the vascular cytokines, IL-6 is well known to be secreted at high levels in human aortic aneurysm disease (13)(14)(15)(16)(17)(18)(19)(20), has been identified as an independent biomarker of severe coronary artery disease (21)(22)(23), and is associated with risk for aneurysm rupture (13-15, 17, 19). Although IL-6 is known to induce systemic production of hepatic acute-phase reactants and facilitate survival of lymphocyte subpopulations (24,25), its local role in aneurysm formation and exacerbation of vascular inflammatory diseases has not been clearly defined.…”

Section: Introductionmentioning

confidence: 99%

An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice

Tieu¹,

Sun²,

LeJeune³

et al. 2009

J. Clin. Invest.

393

375

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Vascular inflammation contributes to cardiovascular diseases such as aortic aneurysm and dissection. However, the precise inflammatory pathways involved have not been clearly defined. We have shown here that subcutaneous infusion of Ang II, a vasopressor known to promote vascular inflammation, into older C57BL/6J mice induced aortic production of the proinflammatory cytokine IL-6 and the monocyte chemoattractant MCP-1. Production of these factors occurred predominantly in the tunica adventitia, along with macrophage recruitment, adventitial expansion, and development of thoracic and suprarenal aortic dissections. In contrast, a reduced incidence of dissections was observed after Ang II infusion into mice lacking either IL-6 or the MCP-1 receptor CCR2. Further analysis revealed that Ang II induced CCR2 + CD14 hi CD11b hi F4/80 -macrophage accumulation selectively in aortic dissections and not in aortas from Il6 -/-mice. Adoptive transfer of Ccr2 +/+ monocytes into Ccr2 -/-mice resulted in selective monocyte uptake into the ascending and suprarenal aorta in regions of enhanced ROS stress, with restoration of IL-6 secretion and increased incidence of dissection. In vitro, coculture of monocytes and aortic adventitial fibroblasts produced MCP-1-and IL-6-enriched conditioned medium that promoted differentiation of monocytes into macrophages, induced CD14 and CD11b upregulation, and induced MCP-1 and MMP-9 expression. These results suggest that leukocyte-fibroblast interactions in the aortic adventitia potentiate IL-6 production, inducing local monocyte recruitment and activation, thereby promoting MCP-1 secretion, vascular inflammation, ECM remodeling, and aortic destabilization.

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“…Furthermore, 70 ascending aortic arch aneurysms, 30 popliteal aneurysms, 23 femoral aneurysms, 22 iliac aneurysms and 10 carotid aneurysms have been collected so far. (27) V alues are numbers of cases with percentages in parentheses or means 8 standard deviations. COPD = Chronic obstructive pulmonary disease; CAD = coronary artery disease; PAD = peripheral artery disease.…”

Section: Interim Resultsmentioning

confidence: 99%

“…Reports regarding an association between serum levels of CRP and AAA presence are also conflicting [25,26] . The most consistent marker associated with AAA is IL-6; showing increased levels in AAA tissue compared to normal aortic wall, increased plasma levels of IL-6 distal from the AAA suggesting IL-6 secretion from the aneurysm and a correlation of plasma IL-6 with aortic diameter in patients without aortic dilatation [27][28][29] . Furthermore, several small studies have shown increased IL-6 levels in the plasma of AAA patients as compared to atherosclerotic or healthy patients [27,[30][31][32] .…”

Section: Discussionmentioning

confidence: 99%

Aneurysm-Express: Human Abdominal Aortic Aneurysm Wall Expression in Relation to Heterogeneity and Vascular Events – Rationale and Design

Hurks¹,

Hoefer

Vink

et al. 2010

Eur Surg Res

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Objective: Elective repair of abdominal aortic aneurysms (AAA) is associated with significant morbidity and mortality. Large amounts of AAA tissue are necessary to assess heterogeneity among AAA and to correct for potential confounders such as known risk factors. The Aneurysm-express study aims to identify different types of AAA using inflammatory markers in the aneurysm wall that predict postoperative cardiovascular adverse events and mortality, therefore allowing individual risk assessment. Methods: The Aneurysm-express is an ongoing prospective cohort study including AAA patients undergoing open repair. At baseline, blood is drawn, relevant clinical data are collected and the standard diagnostic modalities are performed. During surgery a specimen of the ventral AAA wall is collected and processed to study protein expressions and histology. Interim Results: The study commenced in 2003 in 2 medical centers and currently holds information and material of >300 AAA patients, making it the largest reported aneurysm biobank. Patients are followed for 3 years after surgery for occurring cardiovascular events. The current mean follow-up is 2.1 ± 1.3 years with an event rate of 27%. Conclusion: The large amount of structurally stored tissue and blood combined with clinical characteristics and follow-up provide an excellent soil for indepth pathophysiological analyses, with assessment of AAA heterogeneity in combination with postoperative clinical outcome.

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Aortic aneurysms secrete interleukin-6 into the circulation

Cited by 110 publications

References 40 publications

Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma

Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma

An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice

Aneurysm-Express: Human Abdominal Aortic Aneurysm Wall Expression in Relation to Heterogeneity and Vascular Events – Rationale and Design

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