No abstract

These results suggest that IL-7 inflames endothelium via PI3K/AKT-dependent and -independent activation of NF-κB and recruits monocytes/macrophages to the endothelium, thus playing an active role in atherogenesis.

C-reactive protein (CRP) is considered as one of the most sensitive markers of inflammation. The aim of the present study is to investigate the effects of CRP on the production of adiponectin in 3T3-L1 adipocytes. Northern and western blot analysis revealed that CRP treatment inhibited adiponectin mRNA expression and secretion in a dose-and time-dependent manner. Co-incubation of adipocytes with rosiglitazone and CRP decreased induction of adiponectin gene expression by rosiglitazone. However, luciferase reporter assays did not show that CRP affected the activity of w2 . 1 kb adiponectin gene promoter, which was increased by rosiglitazone alone. Pharmacological inhibition of phosphatidylinositol (PI)-3 kinase by LY294002 partially reversed inhibition of adiponectin gene expression by CRP. These results collectively suggest that CRP suppresses adiponectin gene expression partially through the PI-3 kinase pathway, and that decreased production of adiponectin might represent a mechanism by which CRP regulates insulin sensitivity.

No abstract

A reduction in low density lipoprotein (LDL) cholesterol or an increase in high density lipoprotein (HDL) cholesterol can reduce the risk of development of atherosclerosis through overlapping or independent mechanisms. However, the clinical outcome of combined therapy remains in debate. In this study, we first characterized effects of various constructs of helper-dependent adenoviral vector (HDAd) expressing apolipoprotein E3 or LDL receptor (LDLR) in vivo on plasma cholesterol levels. Using this information, we designed experiments and compared the effects of long-term (28 weeks) LDL cholesterol lowering or raising HDL cholesterol, or a combination of both on advanced atherosclerosis in Ldlr −/− mice, a mouse model of familial hypercholesterolemia. Our major findings are: (i) various factors influence in vivo functional activity, which appear to be context dependent; (ii) apolipoprotein AI (APOAI) gene transfer, which raises HDL cholesterol, retards progression of atherosclerosis but does not induce regression; (iii) LDLR or LDLR and APOAI combination gene therapy induces lesion regression; however, LDLR gene transfer accounts for the majority of the effects of combined gene therapy; (iv) LDLR gene therapy reduces interleukin-7, which is a master regulator of T-cell homeostasis, but APOAI gene therapy does not. These results indicate that LDL cholesterol lowering is effective and sufficient in protection against atherosclerosis and induction of regression of preexisting atherosclerosis.