Human Carotid Plaques With High Levels of Interleukin-16 Are Associated With Reduced Risk for Cardiovascular Events.

Abstract

BACKGROUND AND PURPOSE:

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.

• Authors: Caitríona Grönberg, Eva Bengtsson, Gunilla Nordin Fredrikson, Mihaela Nitulescu, Giuseppe Asciutto, Ana Persson, Linda Andersson, Jan Nilsson, Isabel Gonçalves, Harry Björkbacka
• Journal: Stroke (Stroke) Vol. 46 Issue 10 Pg. 2748-54 (Oct 2015) ISSN: 1524-4628 [Electronic] United States
• PMID: 26330445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Biomarkers
• Interleukin-16

Topics

• Aged
• Biomarkers (analysis)
• Carotid Stenosis (complications, immunology)
• Female
• Humans
• Interleukin-16 (analysis, biosynthesis)
• Intracranial Arteriosclerosis (epidemiology, etiology)
• Ischemic Attack, Transient (epidemiology, etiology)
• Male
• Middle Aged
• Polymerase Chain Reaction
• Risk Factors
• Stroke (epidemiology, etiology)