on February 5, 2007
Published online before print February 5, 2007, doi: 10.1161/CIRCULATIONAHA.106.665893
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Submitted on September 20, 2006
From the Research Institute for Internal Medicine (T.B.D., A.Y., A.M., J.K.D., T.U., C.S., S.S.F., P.A., B.H.), Department of Neurology (M.S., A.D., D.R.), Section of Endocrinology (T.U.), Department of Cardiology (E. * To whom correspondence should be addressed. E-mail: bente.halvorsen{at}medisin.uio.no.
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. Methods and 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- 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.
Accepted on January 5, 2007
Increased Expression of Visfatin in Macrophages of Human Unstable Carotid and Coronary Atherosclerosis. Possible Role in Inflammation and Plaque Destabilization
Tuva B. Dahl MSc, 
ie MD, PhD, ., B.B., L.G.), Center for Occupational and Environmental Medicine (S.H.T.), Section of Clinical Immunology and Infectious Diseases (S.S.F., P.A.), Department of Thoracic and Cardiovascular Surgery (K.K.-S.), and Institute for Surgical Research (E..), Rikshospitalet-Radiumhospitalet Medical Center and University of Oslo; and Department of Preventive Cardiology, Ullevål University Hospital and University of Oslo (S.T.), Oslo, Norway.
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- and interleukin-8 levels in peripheral blood mononuclear cells. Both of these effects were abolished when insulin receptor signaling was blocked.
Key words: atherosclerosis • inflammation • leukocytes • plaque • coronary disease
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