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-␣ 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. Conclusions-Our

Stromal stem cells proliferate in vitro and may be differentiated along several lineages. Freshly isolated, these cells have been too few or insufficiently pure to be thoroughly characterized. Here, we have isolated two populations of CD45-CD34+CD105+ cells from human adipose tissue which could be separated based on expression of CD31. Compared with CD31+ cells, CD31- cells overexpressed transcripts associated with cell cycle quiescence and stemness, and transcripts involved in the biology of cartilage, bone, fat, muscle, and neural tissues. In contrast, CD31+ cells overexpressed transcripts associated with endothelium and the major histocompatibility complex class II complex. Clones of CD31- cells could be expanded in vitro and differentiated into cells with characteristics of bone, fat, and neural-like tissue. On culture, transcripts associated with cell cycle quiescence, stemness, certain cytokines and organ specific genes were down-regulated, whereas transcripts associated with signal transduction, cell adhesion, and cytoskeletal +CD105+CD31- cells from human adipose tissue have stromal stem cell properties which may make them useful for tissue engineering.

Background-Inflammation is important in atherogenesis. Interleukin (IL)-1 is the prototypic inflammatory cytokine. We hypothesized a dysbalance between inflammatory and anti-inflammatory mediators in the IL-1 family in coronary artery disease (CAD) and a possible modulation of these mediators by HMG-CoA inhibitors (statins). Methods and Results-In a microarray screening experiment examining peripheral blood mononuclear cells (PBMCs) from 6 CAD patients and 4 healthy control subjects, IL-1␤ was identified as 1 of 25 genes whose expression were upregulated in CAD and downregulated by statins. In the following, we studied the role of IL-1␤ and related mediators in CAD. Our major findings were as follows. (1) Although mRNA levels of IL-1␣ and IL-1␤ were markedly reduced in PBMCs from CAD patients after 6 months of simvastatin (20 mg/d, nϭ15) and atorvastatin (80 mg/d, nϭ15) therapy, the reduction in IL-1 receptor antagonist (IL-1Ra) was more modest. Statins also reduced the spontaneous release of IL-1␤ and IL-1Ra from PBMCs in CAD patients. (2) mRNA levels of IL-1␣, IL-1␤, and IL-1Ra were increased in PBMCs from patients with stable (nϭ20) and unstable (nϭ20) angina compared with healthy control subjects (nϭ15). Although the unstable patients had particularly high levels of IL-1␤ and IL-1␣, IL-1Ra was not correspondingly increased. (3) IL-1␤ induced release of proatherogenic cytokines from PBMCs, whereas atorvastatin partly abolished this effect. Conclusions-Our findings suggest that cytokines in the IL-1 family may represent therapeutic targets in CAD. The ability of statins to modulate these cytokines in an anti-inflammatory direction underscores their immunomodulatory potential.

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