BackgroundAtherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process.MethodsPlasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50–69%) or severe (≥70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined.ResultsOur major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-α in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality.ConclusionOur findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms.

793S troke is one of the major causes of death and disability worldwide. Approximately 85% of all strokes are ischemic, and 20% to 30% of these are caused by carotid atherosclerosis. Moderate-to high-grade carotid artery stenosis can be detected in 1% to 3% of adults, and the incidence increases with age. [1][2][3] Along with the degree of stenosis, inflammation and plaque composition are important in predicting the risk of clinical symptoms. 4 The atherosclerotic plaque is composed of infiltrating inflammatory cells (eg, monocytes/macrophages, T cells, and dendritic cells [DCs]), smooth muscle cells, and lipids. Plaques prone to rupture have thin fibrous caps and high-grade inflammation. The balance between pro-and anti-inflammatory mediators is therefore of major importance for the fate of the plaque and for the occurrence of adverse events. 5,6Background and Purpose-Interleukin (IL)-23 is a cytokine in the IL-12 family, mainly produced by antigen-presenting cells with a central role in inflammation. We hypothesize that IL-23 is also important in atherogenesis and investigate this in a population with carotid atherosclerosis. Methods-Plasma levels of IL-23 were measured in patients with carotid artery stenosis and in healthy controls. The mRNA levels of IL-23 and its receptor, IL-23R, were measured in atherosclerotic plaques, nonatherosclerotic vessels, peripheral blood mononuclear cells, and plasmacytoid dendritic cells. Results-Our findings were as follows: (1) patients with carotid atherosclerosis (n=177) had significantly raised plasma levels of IL-23 when compared with healthy controls (n=24) with particularly high levels in those with the most recent symptoms. (2) mRNA levels of IL-23 and IL-23R were markedly increased in carotid plaques (n=68) when compared with nonatherosclerotic vessels (n=8-10). Immunostaining showed colocalization to plaque macrophages. (3) Patients with carotid atherosclerosis had increased mRNA levels of both IL-23 and IL-23R in plasmacytoid dendritic cells, but not in peripheral blood mononuclear cells. (4) 14-16 Thus, patients with peripheral arterial disease have raised serum levels of IL-23, and increased IL-23 expression is seen in human carotid lesions.14,16 Zhang et al 17 showed that carriers of a polymorphism in the IL-23R gene, which also gave increased expression of IL-23R in peripheral blood mononuclear cells (PBMCs), had increased risk of coronary artery disease. However, decreased IL-23 in PBMCs from patients with coronary artery disease has also been reported. 18 In a mouse model of ischemic stroke, IL-23 levels were upregulated in both the circulation and in the brain. 15 However, the role for IL-23 in atherosclerosis is still unclear.In this study, we examined the expression of IL-23 in patients with carotid atherosclerosis both systemically and within the atherosclerotic plaque as well as its relation to adverse events during follow-up. We also examined the effect of IL-23 in PBMCs and monocytes from patients with carotid atherosclerosis and healthy controls. Mat...

This national study with almost complete inclusion and follow-up shows that the delays occur mainly at patient level and in hospital. The delay is associated with new neurological events. Dual antiplatelet therapy is associated with reduced risk of having a new neurological event before surgery.

Objective/Background: The objective was to observe for 1 year all patients in Norway operated on for symptomatic carotid stenosis with respect to (i) the time from the index event to surgery and neurological events during this time; (ii) the level in the healthcare system causing delay of surgical treatment; and (iii) the possible relationship between peri-operative use of platelet inhibitors and neurological events while awaiting surgery.Methods: This was a prospective national multicentre study of a consecutive series of symptomatic patients. Patients were eligible for inclusion when referred for surgery. An index event was defined as the neurological event prompting contact with the healthcare system. All 15 departments in Norway performing carotid endarterectomy (CEA) participated.Results: Three hundred and seventy one patients were eligible for inclusion between 1 April 2014 and 31 March 2015, and 368 patients (99.2%) were included. Fifty-four percent of the patients contacted their general practitioner on the day of the index event. Primary healthcare referred 84.2% of the patients to hospital on the same day as examined. In hospital median time from admission to referral for vascular surgery was 3 days. Median time between referral to the operating unit and actual CEA was 5 days. Overall, 61.7% of the patients were operated on within 2 weeks of the index event. Twelve patients (3.3%) suffered a new neurological event while awaiting surgery. The percentage of patients on dual antiplatelet therapy was lower (25.0%) in this group than among the other patients (62.6%) (p = .008). The combined 30 day mortality and stroke rate was 3.8%.Conclusion: This national study with almost complete inclusion and follow-up shows that the delays occurs mainly at patient level and in hospital. The delay is associated with new neurological events. Dual antiplatelet therapy is associated with reduced risk of having a new neurological event before surgery.

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