Background-On the basis of our concept that atherosclerosis has an immunopathological background, we tested whether activation of the innate immune system influences its progression. Methods and Results-Hypercholesterolemic (0.5% wt/wt diet) rabbits received either repeated intravenous injections of endotoxin (Escherichia coli lipopolysaccharide 1.25 to 2.5 g, once per week) or a self-limiting cutaneous Staphylococcus aureus infection with or without a quinolone antibiotic. Measured laboratory parameters, including LDL and HDL cholesterols, were similar in the different groups of hypercholesterolemic animals. All endotoxin-treated animals developed transient episodes of fever after endotoxin administration. The extent of atherosclerosis was evaluated by computer-assisted morphometry in the aortas en face (Sudan IV) and by histology at 8 weeks after start of the experiments. Endotoxin-treated animals exhibited significantly accelerated atherosclerosis compared with control animals (141Ϯ38 versus 45Ϯ16 mm 3 total lesion volume, nϭ7 to 9 rabbits each, PϽ0.001). Conclusions-Nonspecific stimulation of the innate immune system accelerates cholesterol-induced atherosclerosis. These data support the concept that atherosclerosis has an immunopathological component and render it improbable that a single infectious agent should assume particular importance in its initiation or progression.
BackgroundCongenital absence of the inferior vena cava (AIVC) is a rare malformation which may be associated with an increased risk for deep vein thrombosis (DVT). However, the role of thrombophilia in AIVC and DVT is unknown.MethodsBetween 1982 and 2013 41 patients (12 female, 29 male, mean age 28 S.D. 11 years) were detected at the University of Düsseldorf, Germany, with AIVC. Based on medical history, clinical examination, imaging and coagulation studies, we performed on this collective a risk characterisation. Extensive literature research added further 123 published cases during 1993 and 2013. AIVC-patients were compared with iliocaval DVT-patients without AIVC (n = 168) treated during the same period in our clinic (90 female, 78 male, mean age 38 S.D. 17 years).ResultsIn contrast to classical DVT younger men were more often affected. Factor-V-Leiden-mutation, 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and hyperhomocysteinemia individually are associated with an increased risk of DVT in patients with AIVC. Aplasia/hypoplasia of the right or left kidney is also associated with IVCA.ConclusionsAIVC should be considered in young patients who present with DVT involving the vena cava. Analysis of publications with AIVC and our patients yielded a typical spectrum of AIVC-associated DVT characteristics: AIVC occurs in young male adults, is revealed by proximal DVT, not necessarily accused by precipitating factors like immobilisation, and is mostly located bilateral. Hereditary coagulation abnormalities seem to be more often a contributing factor for DVT in AIVC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0223-4) contains supplementary material, which is available to authorized users.
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