Objective-To score the number of plaque neutrophils and relate the score to plaque morphology and inflammatory status. Methods and Results-Neutrophils are inflammatory cells with tissue destruction capabilities that have been found at the site of an atherosclerotic plaque rupture or erosion. Poor evidence exists for neutrophil infiltration in human carotid atherosclerotic plaques, and its association with plaque morphology has not yet been described. A set of 355 human carotid plaques was stained for the neutrophil marker CD66b. High neutrophil numbers were found in plaques with a large lipid core, high macrophage numbers, and low collagen amount and smooth muscle cell numbers. High neutrophil numbers were associated with high interleukin 8 (PϽ0.001) and matrix metalloproteases 8 (Pϭ0.005) and 9 (PϽ0.001) plaque levels. High microvessel density within plaques was correlated with high neutrophil numbers (Pϭ0.01). In addition, low numbers of neutrophils were associated with female sex and use of -blockers. Conclusion-For the first time to our knowledge, these results show that neutrophil numbers are strongly associated with the histopathologic features of rupture-prone atherosclerotic lesions and suggest a role for neutrophils in plaque destabilization. (Arterioscler Thromb Vasc Biol. 2010;30:1842-1848.)Key Words: atherosclerosis Ⅲ -adrenergic receptor blockers Ⅲ carotid arteries Ⅲ stroke Ⅲ surgery Ⅲ vascular biology Ⅲ vascular surgery Ⅲ MMP Ⅲ neutrophil C hronic inflammation plays a key role in the pathogenesis and progression of atherosclerosis and, later, in the destabilization and rupture of an atherosclerotic plaque, leading to adverse cardiovascular events. The involvement of inflammatory cells, such as macrophages and T cells, in atherogenesis is well documented, whereas neutrophil granulocytes, also present in atherosclerotic lesions, are detected in much lower numbers.Neutrophils have been observed at the site of plaque erosion or rupture in atherectomy specimens from patients with unstable angina and in autopsy samples from patients with acute myocardial infarction. 1,2 Histological analysis of plaques from cerebral arteries has shown that the expression of neutrophil elastase is increased in late-stage plaques. 3 Epidemiological studies have shown that neutrophil counts in peripheral blood positively correlate with coronary atherosclerotic risk 4 and acute myocardial infarction risk. 5 Mouse studies reveal the accumulation of neutrophils in the luminal plaque region and adventitia of aortic plaques of mice that lack apolipoprotein E 6 and in lesions of low-density lipoprotein receptor-deficient mice. 7 Neutrophils exert most of their functions via preformed granule proteins, mostly found in atherosclerotic lesions (eg, alarmins, human neutrophil peptides, elastase, cathepsin G, and proteinase 3). 8 Neutrophils, similar to monocytes, are phagocytic cells involved in innate immunity. 9 Next to pathogen recognition and destruction, neutrophils contribute to tissue damage by secreting enzymes, such as mye...
Objective-Atherosclerotic cardiovascular disease is a major burden to health care. Because atherosclerosis is considered a systemic disease, we hypothesized that one single atherosclerotic plaque contains ample molecular information that predicts future cardiovascular events in all vascular territories. Methods and Results-AtheroExpress is a biobank collecting atherosclerotic lesions during surgery, with a 3-year follow-up. The composite primary outcome encompasses all cardiovascular events and interventions, eg, cardiovascular death, myocardial infarction, stroke, and endovascular interventions. A proteomics search identified osteopontin as a potential plaque biomarker. Patients undergoing carotid surgery (nϭ574) served as the cohort in which plaque osteopontin levels were examined in relation to their outcome during follow-up and was validated in a cohort of patients undergoing femoral endarterectomy (nϭ151). Comparing the highest quartile of carotid plaque osteopontin levels with quartile 1 showed a hazard ratio for the primary outcome of 3.8 (95% confidence interval, 2.6 -5.9). The outcome did not change after adjustment for plaque characteristics and traditional risk factors (hazard ratio, 3.5; 95% confidence interval, 2.0 -5.9). The femoral validation cohort showed a hazard ratio of 3.8 (95% confidence interval 2.0 to 7.4) comparing osteopontin levels in quartile 4 with quartile 1. Key Words: arterectomy Ⅲ atherosclerosis Ⅲ biomarker Ⅲ plaque A dvanced atherosclerotic cardiovascular disease continues to be a major burden to health care expenditures and requires exhaustive forms of medical treatment. A pressing need exists for prognostic biomarkers to identify high-risk patients for aggressive treatment. Conclusion-PlaqueProteins in the plasma are easily accessible and can serve as a surrogate measure of atherosclerotic disease progression, but existing circulating biomarkers do not provide an accurate value of predictive patient risk. 1,2 The main focus toward identifying patients with rapidly progressive advanced atherosclerotic disease is based on the known characteristics of the vulnerable or recently ruptured plaque with typically a large lipid core, thin fibrous cap, a high number of inflammatory cells, and thrombus. [3][4][5][6] The pathological definition of the vulnerable plaque is founded on cross-sectional studies. Subsequently, molecular and cellular features associated with the vulnerable plaque are considered potential diagnostic imaging markers for plaque rupture and plaque thrombosis. However, longitudinal studies supporting the predictive power of these pathological markers have not been executed, and information about the natural history of atherosclerotic disease is therefore incomplete. The systemic nature of atherosclerotic disease, however, is well-established 7-9 through histopathologic observations demonstrating that inflammation, 10 morphology, 11 and lipid content 12 correlate between different arterial segments within 1 individual. This gave rise to the hypothesis that local plaqu...
The incidence of Type 1 diabetes among 0-14-year-olds in Australia is very high compared with available data from many other countries. The rate of increase observed globally in the last decade has continued well into this decade in Australia. The rising incidence cannot be explained by changes in genetic susceptibility; there is an urgent need to examine the environmental factors that have contributed to this increase. The findings of this study also have important implications for resource planning.
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