Human Carotid Plaques With High Levels of Interleukin-16 Are Associated With Reduced Risk for Cardiovascular Events.
OBJECTIVE
Interleukin-16 (IL-16) functions as a regulator of T-cell growth and acts as an inducer of cell migration. The aim of this study was to determine whether IL-16 measured in human carotid plaques was associated with symptoms (eg, stroke, transient ischemic attack, or amaurosis fugax), markers of plaque stability, and postoperative cardiovascular events.


METHODS
Plaques obtained from patients who had ≥1 cerebrovascular ischemic events within 1 month before endarterectomy (n=111) were compared with plaques from patients without symptoms (n=95). Neutral lipids, smooth muscle cell, and macrophage contents were evaluated histologically, and collagen, elastin, and caspase-3 activity were measured biochemically. IL-16, matrix metalloproteinases, and tissue inhibitors of metalloproteinases were measured in plaque homogenates using a multiplex immunoassay. IL-16, CD3, CD4, and FoxP3 mRNA expressions in carotid plaques were analyzed with quantitative real-time polymerase chain reaction.


RESULTS
Carotid plaques from asymptomatic patients had higher levels of IL-16 mRNA. High plaque IL-16 protein levels (above median) were associated with reduced incidence of postoperative cardiovascular events during a mean follow-up of 21 months (hazard ratio, 0.47; 95% confidence interval, 0.22-0.99; P=0.047). IL-16 levels correlated with the plaque-stabilizing components: elastin, collagen, matrix metalloproteinase-2, tissue inhibitors of metalloproteinase-1, tissue inhibitors of metalloproteinase-2 and FoxP3 mRNA.


CONCLUSIONS
This study shows that high levels of IL-16 are associated with asymptomatic carotid plaques, expression of factors contributing to plaque stability, and decreased risk of new cardiovascular events during a 2-year period after surgery, suggesting that IL-16 might have a protective role in human atherosclerotic disease.
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden. Caitriona.Gronberg@med.lu.se.
Caitríona
C
Grönberg
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Eva
E
Bengtsson
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Gunilla Nordin
GN
Fredrikson
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Mihaela
M
Nitulescu
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Giuseppe
G
Asciutto
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Ana
A
Persson
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Linda
L
Andersson
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Jan
J
Nilsson
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Isabel
I
Gonçalves
From the Department of Clinical Sciences (C.G., E.B., G.N.F., M.N., A.P., L.A., J.N., I.G., H.B.) and Vascular Centre Malmö-Lund (G.A.), Skåne University Hospital, Malmö, Lund University, Lund, Sweden.
Harry
H
Björkbacka
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D016893:Carotid Stenosis / Q000150:complications* / Q000276:immunology*; D005260:Female; D006801:Humans; D019410:Interleukin-16 / Q000032:analysis / Q000096:biosynthesis*; D002537:Intracranial Arteriosclerosis / Q000453:epidemiology* / Q000209:etiology; D002546:Ischemic Attack, Transient / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology
D015415:Biomarkers; D019410:Interleukin-16
atherosclerosis; carotid stenosis; inflammation; interleukin-16; polymerase chain reaction