Background. Aortic dissection still has a poor prognosis despite progress in therapy. Therefore, this prospective follow-up study was designed to determine whether the degree of communication between true and false lumen in relation to the type of dissection, analyzed by transesophageal echocardiography, influences the risk after initiation of medical or surgical therapy.

Background-Simvastatin, a 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor, has been shown to lower serum cholesterol levels in clinical use. Moreover, statins exert beneficial effects in vascular diseases by inhibition of leukocyte rolling, adherence, and transmigration. The aim of this study was to determine if pretreatment with simvastatin attenuates Staphylococcus aureus ␣-toxin-induced increase in leukocyte-endothelial interactions during exotoxemia. Methods and Results-The effects of simvastatin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation. Simvastatin (50 or 100 g/kg) was administered 18 hours before the study. Activation of microcirculation was induced by bolus administration of 40 g/kg S aureus ␣-toxin. Exotoxemia resulted in a significant and time-dependent increase in leukocyte rolling, adherence, and transmigration of leukocytes as well as P-selectin expression on the intestinal vascular endothelium. Pretreatment with simvastatin significantly inhibited exotoxin-induced leukocyte rolling from 71Ϯ10 to 14Ϯ4.7 cells/min (PϽ0.01) and adherence from 14Ϯ3.5 to 0.4Ϯ0.2 cells (PϽ0.01). In addition, simvastatin pretreatment significantly inhibited transmigration of leukocytes from 10.5Ϯ1.2 to 4.2Ϯ0.9 (PϽ0.05) cells. Immunohistochemical detection of endothelial cell adhesion molecule P-selectin showed a 50% decrease in endothelial cell surface expression after simvastatin treatment. Furthermore, simvastatin treatment resulted in enhanced expression of endothelial cell NO synthase III in the intestinal microcirculation. Conclusions-These results demonstrate that simvastatin interferes with exotoxin-induced leukocyte-endothelial cell interactions, which may be relevant in various infectious diseases. Statin treatment may offer a new therapeutic strategy for these clinical conditions.

Abstract-Low-density lipoprotein (LDL) can be transformed to an atherogenic moiety by nonoxidative, enzymatic degradation. Enzymatically degraded LDL induces macrophage foam cell formation, provokes release of cytokines, and also activates complement. To determine whether complement activation may contribute to atherogenesis, 6 pairs of homozygous C6-deficient rabbits and their non-C6-deficient heterozygous siblings were fed a cholesterol-rich diet for 14 weeks. Cholesterol levels and plasma lipoprotein profiles of the animals in the C6-competent and C6-deficient groups did not significantly differ, and the high density lipoprotein and LDL cholesterol ratios at the end of the experiment were 0.07Ϯ0.01 and 0.08Ϯ0.01 (SEM), respectively. However, differences in atherosclerotic plaque formation were discernible macroscopically, with extensive aortic lesions being visible in all C6-competent animals and absent in all C6-deficient animals. Aortas were sectioned from thorax to abdomen, and 10 sections were stained from each aorta. Quantification of atherosclerotic lesions and lumen stenosis with the use of computer-based morphometry documented a dramatic protective effect of C6 deficiency on the development of diet-induced atherosclerosis. We conclude that the terminal complement sequence is centrally involved in atherosclerotic lesion progression. (Arterioscler Thromb Vasc Biol. 1998;18:1790-1795.)Key Words: complement activation Ⅲ atherosclerosis T he possible relevance of complement activation in atherogenesis has not received much attention to date, and only a few reviews are available on the topic. 1,2 The first immunohistochemical studies on complement deposition in atherosclerotic lesions appeared in 1985 to 1987, 3-5 and C5b-9 complexes were subsequently quantified by ELISA in detergent extracts of lesion homogenates. 6 In those studies, the stages of lesion development were not defined, so it could not be excluded that complement activation might have occurred subsequent to tissue damage. An experimental study was then performed in rabbits, leading to the clear demonstration that diet-induced deposition of lipids in the subendothelium was temporally associated with complement activation, which occurred before lesion infiltration by monocytes. 7 A directed search led to tentative identification of the complement-activating entity. Heterogeneously sized lipid droplets containing high amounts of free cholesterol were isolated from early lesions and were shown to be capable of spontaneously activating the alternative complement pathway. 8 The origin of this lipid, termed the lesion complement activator (LCA), was unknown, but the possibility that it represented an LDL derivative was obvious. To corroborate this assumption, attempts were undertaken to transform LDL in vitro into a complement-activating moiety. This was found to be possible by combined treatment of the lipoprotein with a protease, cholesterol-esterase, and neuraminidase, 9 enzymes that occur ubiquitously in lysosomes of mammalian cells and that are...