The placement of endovascular prostheses with graft material incorporating the visceral arteries is safe and appears to be effective at preventing rupture. Continued follow-up to assess the long-term benefit, aneurysm sac behavior and effect of stenting upon the visceral ostia remains critical.

We have previously demonstrated that hexanoyl-D-erythrosphingosine (C 6 -ceramide), an anti-mitogenic cell-permeable lipid metabolite, limited vascular smooth muscle growth by abrogating trauma-induced Akt activity in a stretch injury model of neointimal hyperplasia. Furthermore, ceramide selectively and directly activated protein kinase C (PKC) to suppress Akt-dependent mitogenesis. To further analyze the interaction between ceramide and PKC, the ability of ceramide to localize within highly structured lipid microdomains (rafts) and activate PKC was investigated. Using rat aorta vascular smooth muscle cells (A7r5), we now demonstrate that C 6 -ceramide treatment results in an increased localization and phosphorylation of PKC within caveolin-enriched lipid microdomians to inactivate Akt. In addition, ceramide specifically reduced the association of PKC with 14-3-3, a scaffold protein localized to less structured regions within membranes. Pharmacological disruption of highly structured lipid microdomains resulted in abrogation of ceramide-activated, PKC-dependent Akt inactivation, whereas molecular strategies suggest that ceramide-dependent PKC phosphorylation of Akt3 at Ser 34 was necessary for ceramide-induced vascular smooth muscle cell growth arrest. Taken together, these data demonstrate that structured membrane microdomains are necessary for ceramide-induced activation of PKC and resultant diminished Akt activity, leading to vascular smooth muscle cell growth arrest.

Background-Adipose harbors a large depot of free cholesterol. However, a role for adipose in cholesterol lipidation of high-density lipoprotein (HDL) in vivo is not established. We present the first evidence that adipocytes support transfer of cholesterol to HDL in vivo as well as in vitro and implicate ATP-binding cassette subfamily A member 1 (ABCA1) and scavenger receptor class B type I (SR-BI), but not ATP-binding cassette subfamily G member 1 (ABCG1), cholesterol transporters in this process. Methods and Results-Cholesterol efflux from wild-type, ABCA1Ϫ/Ϫ , SR-BI Ϫ/Ϫ, and ABCG1 Ϫ/Ϫ adipocytes to apolipoprotein A-I (apoA-I) and HDL3 were measured in vitro. 3T3L1 adipocytes, labeled with 3 H-cholesterol, were injected intraperitoneally into wild-type, apoA-I transgenic, and apoA-I Ϫ/Ϫ mice, and tracer movement onto plasma HDL was monitored. Identical studies were performed with labeled wild-type, ABCA1 Ϫ/Ϫ , or SR-BI Ϫ/Ϫ mouse embryonic fibroblast adipocytes. The effect of tumor necrosis factor-␣ on transporter expression and cholesterol efflux was monitored during adipocyte differentiation. Cholesterol efflux to apoA-I and HDL3 was impaired in ABCA1 Ϫ/Ϫ and SR-BI Ϫ/Ϫ adipocytes, respectively, with no effect observed in ABCG1 Ϫ/Ϫ adipocytes. Intraperitoneal injection of labeled 3T3L1 adipocytes resulted in increased HDL-associated 3 H-cholesterol in apoA-I transgenic mice but reduced levels in apoA-I Ϫ/Ϫ animals. Intraperitoneal injection of labeled ABCA1 Ϫ/Ϫ or SR-BI Ϫ/Ϫ adipocytes reduced plasma counts relative to their respective controls. Tumor necrosis factor-␣ reduced both ABCA1 and SR-BI expression and impaired cholesterol efflux from partially differentiated adipocytes. Conclusions-These data suggest a novel metabolic function of adipocytes in promoting cholesterol transfer to HDL in vivo and implicate adipocyte SR-BI and ABCA1, but not ABCG1, in this process. Furthermore, adipocyte modulation of HDL may be impaired in adipose inflammatory disease states such as type 2 diabetes mellitus. Clinical Perspective on p 1355Lipidation of HDL is determined via a number of cholesterol transporters in several cholesterol-rich tissues. Although macrophage cholesterol efflux to HDL plays a major role in attenuating atherosclerosis, macrophages play a minor role in regulation of HDL-C levels. 4 In contrast, hepatic ATPbinding cassette subfamily A member 1 (ABCA1), through lipidation of apolipoprotein A-I (apoA-I), is required for formation of nascent HDL particles. 5 Indeed, in cholesterolrich tissues, both hepatic and extrahepatic, ABCA1 has discrete and essential roles in the maintenance of plasma HDL-C. 6,7 ATP-binding cassette subfamily G member 1 (ABCG1) mediates cholesterol efflux from macrophages to mature HDL particles 8,9 and may play a role in regulating plasma HDL-C levels. 10 In contrast to ABC transporters, scavenger receptor class B type I (SR-BI) is a bidirectional transporter that plays a major role in hepatic uptake of HDL Received July 25, 2009; accepted January 15, 2010. 15,16 In fact, adip...

BackgroundThis paper has two goals. First, we explore the feasibility of conducting online expert panels to facilitate consensus finding among a large number of geographically distributed stakeholders. Second, we test the replicability of panel findings across four panels of different size.MethodWe engaged 119 panelists in an iterative process to identify definitional features of Continuous Quality Improvement (CQI). We conducted four parallel online panels of different size through three one-week phases by using the RAND's ExpertLens process. In Phase I, participants rated potentially definitional CQI features. In Phase II, they discussed rating results online, using asynchronous, anonymous discussion boards. In Phase III, panelists re-rated Phase I features and reported on their experiences as participants.Results66% of invited experts participated in all three phases. 62% of Phase I participants contributed to Phase II discussions and 87% of them completed Phase III. Panel disagreement, measured by the mean absolute deviation from the median (MAD-M), decreased after group feedback and discussion in 36 out of 43 judgments about CQI features. Agreement between the four panels after Phase III was fair (four-way kappa = 0.36); they agreed on the status of five out of eleven CQI features. Results of the post-completion survey suggest that participants were generally satisfied with the online process. Compared to participants in smaller panels, those in larger panels were more likely to agree that they had debated each others' view points.ConclusionIt is feasible to conduct online expert panels intended to facilitate consensus finding among geographically distributed participants. The online approach may be practical for engaging large and diverse groups of stakeholders around a range of health services research topics and can help conduct multiple parallel panels to test for the reproducibility of panel conclusions.