interleukin-8 and Carotid-Stenosis

The aim of this prospective observational registry was to study the outcome of symptomatic patients presenting with recent TIA or minor stroke and severe carotid stenosis, submitted to early percutaneous treatment by stenting. A secondary aim was to evaluate the biological activity of the symptomatic carotid plaques by serial serum and urinary markers (PAPP-A, hs-CRP, MMP-2/MMP-9, IL-6/IL-8, TNF alpha, CD40L) measured by enzyme-linked immunosorbent assay before and after treatment.. From May 2005 to June 2006, 57 patients were enrolled in this prospective registry. All patients underwent carotid stenting using a concentric filter for cerebral protection. The procedure was performed within 24-48hrs of the last attack in patients with TIA (n=24, 42%) and between 14 and 30 days in patients with stroke (n=33, 58%).. Successful stent implantation was achieved in all cases (100%). Adverse events at 1 month were 1 death (1.7%) and 2 TIAs (3.5%). Some of the vulnerability markers, in particular those reflecting an active systemic inflammatory process of the plaque (PAPP-A, hs-CR, and IL-6), were significantly elevated at the time of enrolment, increased after stenting and decreased after 30 days.. Deferred CAS is feasible and safe in selected patients with symptomatic carotid stenosis. This preliminary study in a limited series of patients with unstable carotid plaques revealed that endovascular treatment has a satisfactory outcome considering the very high risk profile of the patient population. The evaluation of some biomarkers suggested an inflammatory role in the process of an unstable carotid plaque generating an acute cerebral event.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Biomarkers; C-Reactive Protein; Carotid Stenosis; CD40 Ligand; Enzyme-Linked Immunosorbent Assay; Feasibility Studies; Female; Humans; Interleukin-6; Interleukin-8; Ischemic Attack, Transient; Italy; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Patient Selection; Pilot Projects; Pregnancy-Associated Plasma Protein-A; Prospective Studies; Prosthesis Design; Registries; Risk Assessment; Severity of Illness Index; Stents; Stroke; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25-30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study.. Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1β, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging.. Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1β, ptrend = 0.03; IL-6, ptrend < 0.0001; IL-8, ptrend = 0.01; interferon (IFN)-γ, ptrend = 0.005; TNF-α, ptrend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01-1.05], p = 0.003).. Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.

Topics: Brain Ischemia; Carotid Artery Diseases; Carotid Stenosis; Clinical Trials as Topic; Cytokines; Humans; Inflammation; Interleukin-6; Interleukin-8; Ischemic Attack, Transient; Ischemic Stroke; Plaque, Atherosclerotic; Prospective Studies; Stroke; Tumor Necrosis Factor-alpha

Several studies suggest a pro-atherogenic role for the CC chemokine receptor 2 (CCR2), thought to reflect interaction with monocyte chemoattractant protein (MCP)-1. Based on its ability to attract leucocytes into inflamed tissue, we hypothesized a pro-atherogenic role for MCP-4, another CCR2 ligand.. Our main findings were: (i) patients with symptomatic carotid stenosis (n = 29), but not those with asymptomatic plaques (n = 31), had significantly raised plasma levels of MCP-4 compared with healthy controls (n = 20); (ii) in vitro, releasate from activated platelets markedly increased the expression of MCP-4 and CCR2 in THP-1 monocytes, and enhanced the MCP-4-mediated effect on interleukin-8 secretion in these cells, involving the platelet-derived chemokine RANTES; (iii) while MCP-1 had no effect on the release of RANTES and interferon-inducible protein of 10 kDa in tumour necrosis factor alpha-pre-activated THP-1 monocytes, MCP-4 profoundly enhanced the release of these pro-atherogenic chemokines; and (iv) the data indicate an inflammatory interaction between RANTES and MCP-4, involving CCR2, and mRNA levels of these mediators were markedly up-regulated within symptomatic atherosclerotic carotid plaque (n = 81).. Our findings suggest that the pro-atherogenic effects of CCR2 may not be restricted to interaction with MCP-1, but could also involve activation by MCP-4, being an inflammatory link between platelet and monocyte activation.

Topics: Aged; Aged, 80 and over; Carotid Stenosis; Case-Control Studies; Cell Line; Chemokine CCL5; Disease Progression; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-8; Male; Middle Aged; Monocyte Chemoattractant Proteins; Monocytes; Platelet Activation; Receptors, CCR2; Severity of Illness Index; Up-Regulation

Inflammation is a key mechanism in human atherosclerotic plaque vulnerability and disruption. The objective was to determine the differential gene expression of pro- and anti-inflammatory factors in the fibrous cap and shoulder region of noncalcified and calcified carotid endarterectomy plaques.. Thirty carotid endarterectomy plaques were classified as type Va (noncalcified, n = 15) and type Vb (calcified, n = 15) in accordance with the American Heart Association consensus. Using laser capture microdissection, fibrous cap and shoulder regions were excised from frozen sections. Gene expression of pro- [interleukin 1 (IL-1), IL-8 and monocyte chemoattractant protein 1 (MCP-1)] and anti-inflammatory (IL-10) factors, and bone formation (bone morphogenetic protein 6 and osteocalcin) mediators were quantitated by real-time PCR. Protein levels were determined using Western blotting.. Mean percent carotid stenosis and calcification area were 79 and 5% in Va-plaques (40% symptomatic) and 77 and 42% in Vb-plaques (20% symptomatic). Macrophages infiltrating the region of the fibrous cap and the shoulder were more numerous in non-calcified plaques compared with calcified plaques (p < 0.01]. mRNA expression of MCP-1 and IL-8, and protein levels of IL-8 were also greater in Va plaques compared to Vb plaques (p < 0.05). Protein levels and mRNA expression of osteocalcin were greater in Vb compared to Va plaques (p < 0.05).. Fibrous cap inflammation is more likely to occur in noncalcified than in calcified plaques. These findings suggest that carotid atherosclerotic plaque calcification is a structural marker of plaque stability.

Topics: Aged; Aged, 80 and over; Biomarkers; Bone Morphogenetic Protein 6; Calcinosis; Carotid Artery Diseases; Carotid Stenosis; Cell Movement; Chemokine CCL2; Cytokines; Endarterectomy, Carotid; Gene Expression Regulation; Humans; Interleukin-10; Interleukin-1beta; Interleukin-8; Macrophages; Middle Aged; Osteocalcin; Retrospective Studies; RNA, Messenger

To compare protein levels of pro-inflammatory factors and bone formation mediators in the fibrous cap and shoulder region of non-calcified and calcified carotid endarterectomy (CEA) plaques.. Twenty-two CEA plaques were classified as non-calcified and calcified groups (n=11 each) in accordance with the American Heart Association (AHA) consensus in 1995. To make frozen sections and H&E staining using plaque, the mean percent of carotid stenosis and calcification area was determined by quantitative histomorphometry. The protein levels of pro-inflammatory interleukin-8 (IL-8), monocyte chematactic protein-1 (MCP-1), bone formation mediators bone morphogenetic protein-6 (BMP-6), and osteocalcin in the fibrous cap and shoulder region of plaques were determined by western blot and were quantified using ImageJ software.. MCP-1 and IL-8 protein were 1.3 (P>0.05) and 1.5 (P<0.05) folds greater in the non-calcified plaques than those in the calcified plaques. BMP-6 and osteocalcin protein were 1.3 (P>0.05) and 2.1 (P<0.01) folds greater in the calcified plaques compared with those of the non-calcified plaques.. Inflammation is more likely to occur in non-calcified carotid plaques, and calcification in the plaques may be associated with bone formation, which indicates that decreased inflammation may be the beginning of calcification in carotid atherosclerotic plaques.

Topics: Atherosclerosis; Bone Morphogenetic Protein 6; Calcinosis; Carotid Stenosis; Chemokine CCL2; Endarterectomy, Carotid; Humans; Inflammation; Interleukin-8

OxLDL uptake and cholesterol efflux inhibition in macrophages play a key role in atherosclerotic plaque formation, rupture, and thrombotic ischemia. This study investigates genes implicated in OxLDL uptake (CD36, SRA), cholesterol efflux inhibition (adipophilin, ADFP), and inflammatory recruitments of leukocytes (IL-8) in plaque lesion areas (PLAs) compared to nonplaque lesion areas (NPLAs) in human carotid endarterectomy specimens. Gene and protein expressions were assayed using quantitative PCR and quantitative immunohistochemistry. Pearson tests were used to investigate potential correlation between (a) different gene expressions and (b) gene expression and patient's plasma constituents. CD36, SRA, ADFP, and IL-8 were shown to be significantly more expressed in PLA compared to NPLA. In PLA, a significant correlation was observed between CD36, SRA, ADFP, and IL-8 mRNA levels. Moreover, CD36 expression level was significantly inversely correlated to plasma marker ApoAI. The above investigated genes/proteins may play a key role in the maturation of atherosclerotic lesions.

Topics: Apolipoprotein A-I; Carotid Stenosis; CD36 Antigens; Cell Line, Tumor; Cholesterol, HDL; Down-Regulation; Endarterectomy, Carotid; Gene Expression; Humans; Interleukin-8; Lipoproteins, LDL; Macrophages; Membrane Proteins; Perilipin-2; RNA, Messenger; Scavenger Receptors, Class A; Up-Regulation

Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) are important factors that induce the migration and proliferation of endothelial cells, increase the vascular permeability, and the modulate chemotaxis of monocytes. These molecules have been found in human atherosclerotic plaques. However, it is not clear whether the circulating levels of IL-8 and VEGF correlate with the extents of carotid stenosis. In this study, we investigated the relationship between circulating levels of IL-8 as well as VEGF and the extents of carotid stenosis. Sera from 41 patients with carotid stenosis were assessed for concentrations of IL-8 and VEGF by enzyme-linked immunosorbent assay. The degree of stenosis of extracranial carotid artery was calibrated by carotid B- mode ultrasonography. The serum concentration of IL-8 (r = -0.04733, p > 0.05) was not correlated with the degree of stenosis. However, the serum concentration of VEGF (r = 0.4974, p < 0.01) was significantly correlated with the degree of carotid stenosis. These findings suggest that increased serum level of VEGF might be a marker for higher degree of stenosis of extracranial carotid artery.

Topics: Adult; Aged; Carotid Artery Diseases; Carotid Stenosis; Disease Progression; Endothelial Growth Factors; Female; Humans; Interleukin-8; Lymphokines; Male; Middle Aged; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors