Systemic and intraplaque mediators of inflammation are increased in patients symptomatic for ischemic stroke.
OBJECTIVE
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 (n=63) or symptomatic (n=18) 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-alpha 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-alpha. Collagen reduction in downstream regions and serum tumor necrosis factor-alpha 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-alpha serum level and intraplaque vulnerability was weak and probably of limited biological importance.
Division of Cardiology, University Hospital Geneva, Faculty of Medicine, Foundation for Medical Researches, Geneva, Switzerland. fabrizio.montecucco@unige.ch
Fabrizio
F
Montecucco
Sébastien
S
Lenglet
Angèle
A
Gayet-Ageron
Maria
M
Bertolotto
Graziano
G
Pelli
Domenico
D
Palombo
Bianca
B
Pane
Giovanni
G
Spinella
Sabine
S
Steffens
Lizzia
L
Raffaghello
Vito
V
Pistoia
Luciano
L
Ottonello
Aldo
A
Pende
Franco
F
Dallegri
François
F
Mach
D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000175:diagnosis; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D020521:Stroke / Q000097:blood* / Q000175:diagnosis
D015415:Biomarkers; D018836:Inflammation Mediators