Objective-Atherosclerosis is considered to be a chronic inflammatory disease and many cytokines participate in the development of atherosclerosis. We focused on the role of interleukin-1 (IL-1), one of the proinflammatory cytokines secreted by monocytes/macrophages, in the progression of atherosclerosis. Methods and Results-We generated mice lacking both apoE and IL-1. The sizes of atherosclerotic lesions at the aortic sinus in apoEϪ/Ϫ/IL-1Ϫ/Ϫmice at 12 and 24 weeks of age showed a significant decrease of approximately 30% compared with apoEϪ/Ϫ/IL-1 ϩ/ϩ mice, and the percentage of the atherosclerotic area to total area of apoEϪ/Ϫ/IL-1Ϫ/Ϫ at 24 weeks of age also showed a significant decrease of about 30% compared with apoEϪ/Ϫ/IL-1 ϩ/ϩ . The mRNA levels of vascular cell adhesion molecule (VCAM)-1 and monocyte chemotactic protein-1 in the apoEϪ/Ϫ/ IL-1Ϫ/Ϫ aorta were significantly reduced compared with the apoEϪ/Ϫ/IL-1 ϩ/ϩ . Furthermore, VCAM-1 was also reduced at the protein level in apoEϪ/Ϫ/IL-1Ϫ/Ϫ aorta compared with apoEϪ/Ϫ/IL-1 ϩ/ϩ .
Conclusions-The
These findings demonstrate that IFN-gamma produced by bone marrow-derived cells delays the progression of atherosclerosis without any effect on plasma lipids, and this suppression may be due to decreased extracellular matrix deposition.
Background: The purpose of this study was to evaluate the performance of two homogeneous assays for LDL-cholesterol (LDL-C), a polyethylene/cyclodextrin (PC) assay and a detergent (D) assay, which are based on different principles, in cholestatic serum.
Methods: We compared serum LDL-C concentrations determined by the two assays for healthy normolipidemic subjects (n = 42) and cholestatic patients (n = 51). LDL-C concentrations obtained with the homogeneous assays were also compared with those obtained by HPLC for patients’ sera. In the interference study, conjugated bile acids were added to normal serum, and their effects on the two assays were examined. The effects of lipoprotein-X (LP-X), intermediate-density lipoprotein (IDL), and apolipoprotein (apo) E-rich HDL on the LDL-C assays were also investigated by adding these lipoproteins to normal serum.
Results: The LDL-C concentrations obtained with the D assay were higher than those obtained with the PC assay in the serum with high LP-X. The bias for LDL-C vs LP-X in cholestatic serum correlated with LP-X concentration (r = 0.582; P <0.0001; n = 51). In the interference study, no effect of bile acids on the LDL-C assays was observed. However, the D assay measured 51.0% of the cholesterol in LP-X, whereas no reactivity was observed for LP-X in the PC assay. In addition, the D assay and the PC assay measured IDL-cholesterol at 31.2% and 52.4%, respectively, and measured apo E-rich HDL-C at 7.6% and 17.8%, respectively.
Conclusions: Although both homogeneous LDL-C assays are suitable for most cases, the present study showed that each homogeneous assay has a different limitation for cholestatic serum with gross alterations in lipoproteins.
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