Hypercholesterolemic human LDL contains oxidized subfractions that have atherogenic properties. Paradoxically, atherosclerosis incidence is low in patients with primary biliary cirrhosis (PBC), a disease characterized by marked increases in plasma LDL, including the LDL subfraction lipoprotein-X (Lp-X). To investigate the mechanisms underlying this paradox, we first examined the propensity to oxidation of unfractionated LDL isolated from PBC patients. After prolonged incubation with copper, PBC-LDL failed to increase the oxidation index or electrophoretic mobility noted in control LDL. An admixture of PBC-LDL or Lp-X with control LDL prevented oxidation of the latter in a dose-dependent manner. PBC-LDL was also noncompetitive against copper-oxidized LDL (oxLDL) for binding with a murine monoclonal anti-oxLDL antibody in a competitive ELISA. OxLDL exerts its proapoptotic and antiangiogenic effects in part by inhibiting fibroblast growth factor 2 (FGF2) expression. Preincubation of oxLDL with PBC-LDL, but not control LDL, attenuated the inhibitory effects of oxLDL on FGF2 expression in cultured bovine aortic endothelial cells (ECs). The antioxidant and prosurvival properties of PBC-LDL diminished after the patients underwent orthotopic liver transplantation. These results suggest that Lp-X reduces LDL atherogenicity by preventing LDL oxidation to protect EC integrity in the presence of hypercholesterolemia. They also suggest that altering LDL composition may be as important as reducing LDL concentration in preventing or treating atherosclerosis. -Chang, P-Y., S-C. Lu, T-C. Su, S-F. Chou, W-H. Huang, J. D. Morrisett, C-H. Chen, C-S. Liau, and Y-T. Lee. Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation.

Several large-scale epidemiological and intervention studies strongly indicate that postchallenge hyperglycaemia is the main factor associated with increasing the risk of morbidity and mortality in type 2 diabetes. However, the mechanisms that increase the risk of cardiovascular disease remain unclear. We aimed to study the relationship between postchallenge hyperglycaemia and arterial stiffness. We recruited 40 healthy subjects from a physical examination in 2005. Cardio-ankle vascular index (CAVI) was automatically calculated by VaSera VS-1000. For the reliability study, we performed the baseline study in the first 20 subjects who were returned to receive repeated measurements of CAVI 2 weeks later. The determinants of mean CAVI at different timings of oral glucose tolerance test (OGTT) study were analysed by constructing multivariate linear regression models. In reliability test, the inter-observer correlation coefficient was 0.82 for right CAVI, 0.87 for left CAVI and 0.85 for mean CAVI. Age, systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose levels at 60 min (Glu60) and glucose area under the curve of OGTT (GluAUC) are found to be significantly and positively correlated to right CAVI, left CAVI and mean CAVI (p < 0.05). After adjustment for age, gender and SBP, Glu60 and GluAUC are still independent determinants of CAVI. In subjects without clinical diagnosis of type 2 diabetes, postchallenge hyperglycaemic spike is highly associated with CAVI, a good parameter of aortic stiffness, independent of age, gender and blood pressure.

Adiponectin can protect vessels from injury by promoting the activity of endothelial nitric oxide synthase (eNOS) with increased nitric oxide production. Recently, it was demonstrated that eNOS activity is highly regulated by heat shock protein 90 (HSP90). We tested the hypothesis that adiponectin can prevent endothelial cell injury produced by angiotensin II through promotion of the association between eNOS and HSP90. Cultured human umbilical vein endothelial cells (HUVECs) were treated with angiotensin II (2 lM) to induce apoptosis. In the presence of globular adiponectin, apoptosis was inhibited in a dose-response manner. Angiotensin II-induced apoptosis was also inhibited by treatment with an NO donor and by combined treatment with both angiotensin II type 1 and type 2 receptor blockers. Western blotting and immunoprecipitation of the lysates from the treated cells showed that globular adiponectin could restore the association between eNOS and HSP90 and enhance the phosphorylation of eNOS. In conclusion, angiotensin II-induced human endothelial cell apoptosis can be prevented by adiponectin through promotion and stabilization of the association between eNOS and HSP90.

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