Characterisation of Interleukin-8 and Monocyte Chemoattractant Protein-1 Expression within the Abdominal Aortic Aneurysm and their Association with Mural Inflammation

Middleton, R.K.; Bown, MJ; Lloyd, Geraint; Jones, J. Louise; London, N. J. M.; Sayers, Robert D.

doi:10.1016/j.jvs.2008.11.106

Cited by 11 publications

(24 citation statements)

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“…More specifically, monocyte/macrophages have been extensively studied in the initiation and progression of AAA, 31,32 and knockout of the MCP-1 receptor, CCR-2, can abrogate murine aneurysm growth. 33 Having demonstrated in vitro that IL-6 induces MCP-1 production from VSMCs and that the system is STAT3 dependent, this project went on to localize and quantify aortic macrophages by 2 different methods.…”

Section: Discussionmentioning

confidence: 99%

Elevated Wall Tension Initiates Interleukin-6 Expression and Abdominal Aortic Dilation

Akerman

Stroud

Barrs

et al. 2018

Annals of Vascular Surgery

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Background Hypertension (HTN) has long been associated with abdominal aortic aneurysm (AAA) development, and these cardiovascular pathologies are biochemically characterized by elevated plasma levels of angiotensin II (AngII) as well as interleukin-6 (IL-6). A biologic relationship between HTN and AAA has not been established, however. Accordingly, the objective of this study was to evaluate whether elevated tension may initiate IL-6 production to accumulate monocyte/macrophages and promote dilation of the abdominal aorta (AA). Methods An IL-6 infusion model (4.36 µg/kg/day) was created utilizing an osmotic infusion pump, and after 4 weeks, AA diameter was measured by digital microscopy. The AA was then excised for CD68 immunostaining and flow cytometric analysis with CD11b and F4/80 to identify macrophages. Aortic segments from wild-type mice were suspended on parallel wires in an ex vivo tissue myograph at experimentally derived optimal tension (1.2 g) and in the presence of elevated tension (ET, 1.7 g) for 3 hr, and expression of IL-6 and monocyte chemoattractant protein-1 (MCP-1) was evaluated by quantitative polymerase chain reaction (QPCR). Isolated aortic vascular smooth muscle cells (VSMCs) were subjected to 12% biaxial cyclic stretch or held static (control) for 3 hr (n = 7), and IL-6 and MCP-1 expressions were evaluated by QPCR. Results Four-week IL-6 infusion resulted in an AA outer diameter that was 72.5 ± 5.6% (P < 0.05) greater than that of control mice, and aortic dilation was accompanied by an accumulation of macrophages in the AA medial layer as defined by an increase in CD68 + staining as well as an increase by flow cytometric quantification of CD11b+/F4/80+ cells. Wild-type AA segments did not respond to ex vivo application of ET but cyclic stretch of isolated VSMCs increased IL-6 (2.03 ± 0.3 fold) and MCP-1 (1.51 ± 0.11 fold) expression compared to static control (P < 0.05). Pretreatment with the selective STAT3 inhibitor WP1066 blunted the response in both cases. Interestingly, AngII did not stimulate expression of IL-6 and MCP-1 above that initiated by tension and again, the response was inhibited by WP1066, supporting an integral role of STAT3 in this pathway. Conclusions An IL-6 infusion model can initiate macrophage accumulation as well as aortic dilation, and under conditions of elevated tension, this proinflammatory cytokine can be produced by aortic VSMCs. By activation of STAT3, MCP-1 is expressed to increase media macrophage abundance and create an environment susceptible to dilation. This biomechanical association between HTN and aortic dilation may allow for the identification of novel therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Elevated Wall Tension Initiates Interleukin-6 Expression and Abdominal Aortic Dilation

Akerman

Stroud

Barrs

et al. 2018

Annals of Vascular Surgery

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“…A total of 239 papers were identified from these searches and the corresponding abstracts were read to identify those studies appropriate for inclusion. This two stage search strategy identified 2 new papers not previously included [9,19].…”

Section: Search Strategymentioning

confidence: 99%

A Systematic Review of Studies Examining Inflammation Associated Cytokines in Human Abdominal Aortic Aneurysm Samples

et al. 2009

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Objectives: Inflammation is critical in abdominal aortic aneurysm (AAA) but there is no current consensus on which inflammation related cytokines are important. The aim of this review was to systemically assess previous studies investigating the relative expression of inflammation associated cytokines within human AAA samples. Methods: The MEDLINE database was searched for studies which simultaneously examined an array of different inflammation associated cytokines in aortic samples in order to identify those associated with AAA. Focused searches were then conducted for further studies assessing relative concentrations of these cytokines in aortic samples in relation to AAA. Appropriate studies were assessed by two reviewers independently. Results: Eighteen studies were included. A number of different cytokines have been consistently found to be upregulated within AAA by comparison to aortic samples removed from patients without cardiovascular disease, however findings relative to samples of aortic athero-thrombosis were less consistent. TNFA and INFG appear to be the most consistently associated with AAA in studies using both normal and atherosclerotic controls. Cautious interpretation of these data is recommended due to a number of methodological problems. Conclusions: This systematic review suggests that TNFA and INFG are the most consistently upregulated cytokines in large AAAs. Further studies utilizing larger populations, new proteomic techniques and better patient matching are required.

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“…, 2009). Pro‐inflammatory cytokines such as TNFα and TNFβ are found in increased amounts in aneurysm walls, along with infiltrates of inflammatory cells (Middleton et al. , 2009; Wallinder et al.…”

Section: Introductionmentioning

confidence: 99%

“…Autoimmunity, chronic infection and cigarette smoking may account for the presence and persistence of inflammation (Hirose & Tilson, 2001;Jagadesham et al, 2008;Arapoglou et al, 2009). Pro-inflamma-tory cytokines such as TNFa and TNFb are found in increased amounts in aneurysm walls, along with infiltrates of inflammatory cells (Middleton et al, 2009;Wallinder et al, 2009). These lymphocytes and macrophages produce matrix metalloproteinases (MMPs), causing enzymatic degradation of collagen and expansion of the weakened aorta (Jacob, 2003).…”

Section: Introductionmentioning

confidence: 99%

Coding polymorphisms in the genes of the alternative complement pathway and abdominal aortic aneurysm

Bradley

Badger

Bown

et al. 2011

International Journal of Immunogenetics

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Variants in the genes of the alternative complement pathway are associated with risk of numerous inflammatory diseases. Abdominal aortic aneurysm is associated with inflammation and is a common cause of illness and death among European populations. This study tested 49 single nucleotide polymorphisms, including common putatively functional polymorphisms, in the genes of the alternative complement cascade (CFH, CFB, CFD, CFI, properdin, CR1, CR1L, CR2, CD46, vitronectin, C3, C5, C6, C7, C8A, C8B, C8G and C9). The study group were 434 cases with infra-renal aortic diameter ≥30 mm and 378 disease-free controls from two UK centres, all with self-reported European ancestry. There was no evidence for significant association with presence or size of aneurysm following correction for multiple testing. This study suggests that variation in the genes of the alternative pathway is not an important cause of abdominal aortic aneurysm development.

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Characterisation of Interleukin-8 and Monocyte Chemoattractant Protein-1 Expression within the Abdominal Aortic Aneurysm and their Association with Mural Inflammation

Cited by 11 publications

References 0 publications

Elevated Wall Tension Initiates Interleukin-6 Expression and Abdominal Aortic Dilation

Elevated Wall Tension Initiates Interleukin-6 Expression and Abdominal Aortic Dilation

A Systematic Review of Studies Examining Inflammation Associated Cytokines in Human Abdominal Aortic Aneurysm Samples

Coding polymorphisms in the genes of the alternative complement pathway and abdominal aortic aneurysm

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