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, Matthew J.; Lloyd, Geraint; Jones, J. Louise; London, N. J. M.; Sayers, Robert D.

doi:10.1016/j.ejvs.2008.09.013

Cited by 23 publications

(11 citation statements)

References 24 publications

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“…We also found that inflammatory molecules and macrophage infiltration were increased in the aneurysmal wall. MCP-1 is a major factor promoting the accumulation of macrophages in atherosclerosis 25 and abdominal aortic aneurysms, 26 and it is involved in the patho- We demonstrated that MR activation with DOCA resulted in a high incidence of cerebral aneurysms, and the mRNA levels of oxidative stress and inflammatory genes were increased despite a moderate increase in blood pressure. Oxidative stress and inflammation are associated with RAS activation.…”

Section: Discussionmentioning

confidence: 99%

Role of Mineralocorticoid Receptor on Experimental Cerebral Aneurysms in Rats

et al. 2009

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Abstract-Activation of the renin-angiotensin (Ang)-aldosterone system is involved in the pathology of vascular diseases.Although the blockade of the mineralocorticoid receptor protects against vascular diseases, its role in cerebral aneurysms remains to be elucidated. We treated female rats subjected to renal hypertension, increased hemodynamic stress, and estrogen deficiency for 3 months with the mineralocorticoid receptor blocker eplerenone (30 or 100 mg/kg per day) or vehicle (vehicle control). Eplerenone reduced the incidence of cerebral aneurysms and saline intake without lowering of the blood pressure. In the aneurysmal wall, the production of Ang II and nitrotyrosine was increased. The mRNA levels of Ang-converting enzyme 1 and NADPH oxidase subunits NOX4, Rac1, monocyte chemoattractant protein 1, and matrix metalloproteinase 9 were increased. Eplerenone brought about a reduction in these molecules, suggesting that mineralocorticoid receptor blockade suppresses cerebral aneurysm formation by inhibiting oxidative stress, inflammatory factors, local renin-Ang system activation, and saline intake. Other female rats implanted with pellets of the mineralocorticoid receptor agonist deoxycorticosterone acetate manifested a high incidence of cerebral aneurysm formation and the upregulation of molecules related to oxidative stress, inflammatory factors, and the local renin-Ang system; their saline intake was increased. We demonstrate that mineralocorticoid receptor activation at least partly contributes to the pathogenesis of cerebral aneurysms. (Hypertension. 2009;54:552-557.)Key Words: cerebral Ⅲ aneurysm Ⅲ inflammation Ⅲ mineralocorticoid receptor Ⅲ oxidative stress R upture of cerebral artery aneurysms results in catastrophic subarachnoid hemorrhage and a high risk for morbidity and mortality. 1 On the basis of epidemiological data showing a high incidence of cerebral aneurysms in postmenopausal women, we subjected female rats to increased hemodynamic stress, hypertension, and estrogen deficiency (by oophorectomy); in these animals, the incidence of cerebral aneurysms was high. 2 Treatment with 17␤-estradiol or an angiotensin (Ang) II type 1 receptor blocker reduced this incidence. 2 Elsewhere we suggested that endothelial injury is an initial event in the pathogenesis of cerebral aneurysms and that an increase in Ang II and NADPH oxidase subunits is involved. 2 Also, inflammation and degradation of the extracellular matrix in the vascular wall play a role in the development of cerebral aneurysms. [3][4][5] The renin-Ang-aldosterone system is involved in the pathophysiology of cardiovascular and kidney diseases, activation of the mineralocorticoid receptor (MR) is especially highlighted in recent studies. 6 -10 The identification of a new site of MR expression in nonepithelial tissues, such as the heart, 11 vasculature, 12 and brain, 13 suggested the presence in these tissues of potential new MR target genes with unexpected biological functions. In aortic endothelial cells, aldosterone increased the express...

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Section: Discussionmentioning

confidence: 99%

Role of Mineralocorticoid Receptor on Experimental Cerebral Aneurysms in Rats

et al. 2009

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“…22 Loss of function of DPPI resulted in a diminished recruitment of neutrophils to the elastase-injured aorta and an impaired production of CXC-chemokine ligand 2. 22 The role of neutrophils in AAA pathogenesis can be further reinforced by the finding that IL-8, a CXC chemokine involved in neutrophil chemotaxis and degranulation, 18 is increased in the plasma 77 and the aortic wall 18,63 of patients with AAA.…”

Section: Polymorphonuclear Leukocytesmentioning

confidence: 93%

Immune Cells and Molecular Mediators in the Pathogenesis of the Abdominal Aortic Aneurysm

Rizas

Ippagunta²,

Tilson³

2009

Cardiology in Review

135

105

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Abdominal aortic aneurysm is a multifactorial disease with genetic risk factors and an immunologic component. Immune cells, including macrophages, neutrophils, mast cells, B- and T- lymphocytes, along with vascular smooth muscle cells and adventitial fibroblasts, produce cytokines and enzymes, promoting an inflammatory reaction, extracellular matrix degradation, and neovascularization. Among the different enzymes secreted by immune and stromal cells, matrix metalloproteinase (MMP)-2, MMP-9, MMP-12, cathepsins, and neutrophil elastase cause medial degeneration. Chymase causes smooth muscle cell apoptosis, and MMP-3, MMP-8, and MMP-13 cause adventitial collagen degradation, promoting abdominal aortic aneurysm rupture. At the same time chemokines (interleukin 8, macrophage inflammatory protein 1 alpha, monocyte chemotactic protein-1) cause recruitment and proliferation of inflammatory cells, whereas cytokines (vascular endothelial growth factor and transforming growth factor-beta) promote neoangiogenesis.

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“…The protein, consisting of 72 amino acids in its mature form, is identified as a basic and heparin-binding protein [7,9,11,12]. IL-8 also exhibits chemotactic activities against T lymphocytes and basophils, as well as neutrophils in vitro [9,10].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the direct hepatic effects of intramuscular interleukin-8 injection in an experimental rabbit model

Kestelli

Guzeloglu

Yurekli

et al. 2013

Med Sci Monit Basic Res

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BackgroundThe aim of this study was to investigate the effects of intramuscular IL-8 injection on hepatic tissues using an in vivo histopathological animal model.Material/MethodsTwelve New Zealand white rabbits were used for this randomized, controlled, single-blinded interventional study. For 6 days, 1 gluteus maximus muscle was injected daily with 1 mcg/kg of IL-8 in 6 rabbits (Group A). The remaining 6 rabbits (to determine to normal porto-hepatic morphology of the rabbit genus) were in the sham group (Group B). At the end of the 7th day, all rabbits were killed and livers were meticulously harvested. Microscopically, regional tissues were scored according to portal inflammation, focal necrosis, piecemeal necrosis, and total impact.ResultsTotal impact score, portal inflammation, focal necrosis, and piecemeal necrosis were the histopathologic changes present in a higher incidence in the IL-8 group compared with the control group. The differences were significant when the groups were compared according to total impact score, portal inflammation, focal necrosis, and piecemeal necrosis according to Pearson’s correlation (p<0.05). The most significant differences were detected at the total impact scores (p=0.002) and the portal inflammation scores (p=0.008).ConclusionsOur results showed that IL-8 may damage hepatocytes. This can be the determined target for new therapeutic strategies. Further trials should be designed to obtain definitive results.

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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

Abstract: Pathways involving IL-8 and MCP-1 may be involved in AAA pathogenesis. IL-8 may be directly involved in the chemotaxis of T(H)-lymphocytes into the AAA wall.

Cited by 23 publications

References 24 publications

Role of Mineralocorticoid Receptor on Experimental Cerebral Aneurysms in Rats

Role of Mineralocorticoid Receptor on Experimental Cerebral Aneurysms in Rats

Immune Cells and Molecular Mediators in the Pathogenesis of the Abdominal Aortic Aneurysm

Investigation of the direct hepatic effects of intramuscular interleukin-8 injection in an experimental rabbit model

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