Systemic and Intraplaque Mediators of Inflammation Are Increased in Patients Symptomatic for Ischemic Stroke

Abstract

Background and Purpose-The concept of "vulnerable plaque" has been extended to the more recent definition of the "cardiovascular vulnerable patient," in which "intraplaque" and "systemic" factors contribute to the cumulative risk of acute cardiovascular events. Thus, we investigated the possible role of systemic and intraplaque inflammation in patients asymptomatic versus symptomatic for ischemic stroke. Methods-Regions upstream and downstream the blood flow were isolated from internal carotid plaques of patients asymptomatic (nϭ63) or symptomatic (nϭ18) for ischemic stroke. Specimens were analyzed for lipid, collagen, macrophage, lymphocyte, neutrophil, mast cell and smooth muscle cell content, and chemokine and cytokine mRNA expression. Chemokine receptors and adhesion molecules were assessed on circulating leukocytes by flow cytometry. Systemic inflammatory markers and biochemical parameters were measured on total blood, plasma, and serum. Results-Tumor necrosis factor-␣ and CCL5 serum levels as well as intercellular adhesion molecule-1 expression on circulating neutrophils were increased in symptomatic as compared with asymptomatic patients. Collagen content and smooth muscle cell infiltration were decreased in symptomatic plaques. In upstream regions of symptomatic plaques, lipid content and lymphocyte infiltration were increased. In downstream regions of symptomatic plaques, macrophage, neutrophil, and mast cell infiltration were increased. Intraplaque collagen content was positively correlated with smooth muscle cell infiltration and inversely correlated with macrophages, neutrophils, or serum tumor necrosis factor-␣. Collagen reduction in downstream regions and serum tumor necrosis factor-␣ were independently associated with the likelihood of being symptomatic. Conclusions-Inflammatory mediators are increased in ischemic stroke. Despite statistically significant, the correlation between tumor necrosis factor-␣ serum level and intraplaque vulnerability was weak and probably of limited biological importance. (Stroke. 2010;41:1394-1404.)Key Words: carotid artery Ⅲ carotid endarterectomy Ⅲ inflammation Ⅲ leukocytes V ariations in plaque composition, size, and severity of lumen stenosis have been identified as crucial aspects of plaque vulnerability. 1,2 Inflammation, thin or fissured cap with large lipid core, and severe stenosis increase plaque vulnerability. In addition, superficial calcified nodules, hemorrhages, endothelial dysfunction, and expansive (positive) remodeling could also contribute to atherosclerotic plaque destabilization. More recently, clinical studies suggested that acute ischemic events could be also influenced by systemic factors and peripheral tissue resistance to hypoxia. 3 Nonspecific serum markers of altered lipid profile, inflammation, and hypercoagulability have been identified. 4 Thus, the concept of "vulnerable plaque" has been extended to the more recent definition of the "cardiovascular vulnerable patient," in which "intraplaque" and systemic factors contribute to the cumulati...

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Acipimox reduces circulating levels of insulin and associated neutrophilic inflammation in metabolic syndrome

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