Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization.
BACKGROUND
Although the participation of inflammation in atherogenesis is widely recognized, the identification of the different components has not been clarified. In particular, the role of inflammation in plaque destabilization is not fully understood.


RESULTS
Our main findings were as follows: (1) In a microarray experiment, we identified visfatin, one of the most recently identified adipokines, as a gene that was markedly enhanced in carotid plaques from symptomatic compared with plaques from asymptomatic individuals. This finding was confirmed when carotid plaques from 7 patients with asymptomatic and 14 patients with symptomatic lesions were examined with real-time reverse transcription polymerase chain reaction. (2) Immunohistochemistry showed that visfatin was localized in areas that were rich in lipid-loaded macrophages. (3) The relationship between visfatin and unstable lesions was also found in patients with coronary artery disease, demonstrating a strong visfatin immunostaining in lipid-rich regions within the material obtained at the site of plaque rupture in patients with acute myocardial infarction. (4) Both oxidized low-density lipoprotein and tumor necrosis factor-alpha increased visfatin expression in THP-1 monocytes, with a particularly enhancing effect when these stimuli were combined. (5) Visfatin increased matrix metalloproteinase-9 activity in THP-1 monocytes and tumor necrosis factor-alpha and interleukin-8 levels in peripheral blood mononuclear cells. Both of these effects were abolished when insulin receptor signaling was blocked.


CONCLUSIONS
Our findings suggest that visfatin should be regarded as an inflammatory mediator, localized to foam cell macrophages within unstable atherosclerotic lesions, that potentially plays a role in plaque destabilization.
Dahl
Tuva B
TB
Research Institute for Internal Medicine, Rikshospitalet-Radiumhospitalet Medical Center and University of Oslo, N-0027 Oslo, Norway.
Yndestad
Arne
A
Skjelland
Mona
M
Øie
Erik
E
Dahl
Arve
A
Michelsen
Annika
A
Damås
Jan K
JK
Tunheim
Siv H
SH
Ueland
Thor
T
Smith
Camilla
C
Bendz
Bjørn
B
Tonstad
Serena
S
Gullestad
Lars
L
Frøland
Stig S
SS
Krohg-Sørensen
Kirsten
K
Russell
David
D
Aukrust
Pål
P
Halvorsen
Bente
B
D000368:Aged; D000789:Angina, Unstable / Q000276:immunology; D050197:Atherosclerosis / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000378:metabolism*; D002460:Cell Line; D003324:Coronary Artery Disease / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology*; D016209:Interleukin-8 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D020780:Matrix Metalloproteinase 9