Recent epidemiological and clinical data show protection from CVD (cardiovascular disease), all-cause mortality and cancer in subjects with GS (Gilbert's syndrome), which is characterized by a mildly elevated blood bilirubin concentration. The established antioxidant effect of bilirubin, however, contributes only in part to this protection. Therefore we investigated whether mildly elevated circulating UCB (unconjugated bilirubin) is associated with altered lipid metabolism. The study was performed on GS and age- and gender-matched healthy subjects ( n =59 per group). Full lipoprotein profile, TAG (triacylglycerols), Apo (apolipoprotein)-A1, Apo-B, lipoprotein(a), the subfractions of LDL (low-density lipoprotein) and selected pro-inflammatory mediators were analysed. A hyperbilirubinaemic rodent model (Gunn rats, n =40) was investigated to further support the presented human data. GS subjects had significantly ( P <0.05) improved lipid profile with reduced total cholesterol, LDL-C (LDL-cholesterol), TAG, low- and pro-atherogenic LDL subfractions (LDL-1+LDL-2), Apo-B, Apo-B/Apo-A1 ratio and lower IL-6 (interleukin 6) and SAA (serum amyloid A) concentrations ( P =0.094). When the control and GS groups were subdivided into younger and older cohorts, older GS subjects demonstrated reduced lipid variables (total cholesterol and LDL-C, TAG and LDL-C subfractions, Apo-B/Apo-A1 ratio; P <0.05; Apo-B: P <0.1) compared with controls. These data were supported by lipid analyses in the rodent model showing that Gunn rat serum had lower total cholesterol (2.29±0.38 compared with 1.27±0.72 mM; P <0.001) and TAG (1.66±0.67 compared with 0.99±0.52 mM; P <0.001) concentrations compared with controls. These findings indicate that the altered lipid profile and the reduced pro-inflammatory status in hyperbilirubinaemic subjects, particularly in the older individuals, probably contribute additionally to the commonly accepted beneficial antioxidant effects of bilirubin in humans.

The aim of the present study was to assess circulating levels of VEGF (vascular endothelial growth factor), a biomarker with prognostic significance in cardiovascular disease, and markers of systemic inflammation in patients with stable and exacerbated COPD (chronic obstructive pulmonary disease). Lung function parameters, arterial blood gas analysis and circulating levels of VEGF, IL-6 (interleukin-6), TNF-α (tumour necrosis factor-α), CRP (C-reactive protein), fibrinogen and the peripheral blood neutrophil cell count were assessed in 30 patients on admission to the hospital for acute exacerbation of COPD, in 30 age-, gender- and BMI (body mass index)-matched patients with stable COPD, and 30 matched controls with normal lung function. Patients with acute exacerbated COPD had higher circulating concentrations of VEGF ( P <0.001), IL-6 ( P <0.05) and CRP ( P <0.01) and an increased blood neutrophil cell count ( P <0.05) compared with patients with stable COPD and healthy controls. VEGF levels in exacerbated COPD correlated with systemic inflammatory markers, such as CRP ( r =0.61, P <0.005), IL-6 ( r =0.46; P <0.01) and fibrinogen ( r =0.39, P <0.05). In patients with stable COPD, there was a significant relationship between circulating VEGF levels and the percentage of the predicted FEV 1 (forced expiratory volume in 1 s) ( r =0.47, P <0.01). Recovery from the exacerbation resulted in a significant decrease in both circulating VEGF levels and markers of systemic inflammation. In conclusion, circulating levels of VEGF and markers of systemic inflammation are up-regulated in patients with acute exacerbated COPD and decrease after recovery from the exacerbation.

Acute inflammation impairs vascular function. Based on the association between endothelial dysfunction and plasma concentrations of L -arginine and the endogenous nitric oxide synthase inhibitor ADMA (asymmetrical dimethylarginine), we hypothesized that the ratio between L -arginine and ADMA could be affected by experimental inflammation. Plasma concentrations of L -arginine, ADMA and SDMA (symmetrical dimethylarginine) were studied at baseline and 3.5 h after intravenous administration of Escherichia coli endotoxin [LPS (lipopolysaccharide), 20 units/kg of body mass; n =8] or placebo ( n =9) in healthy males. L -Arginine and dimethylarginines were quantified after solid-phase extraction by reversed-phase HPLC. Body temperature, heart rate and leucocyte count increased after LPS administration ( P <0.01 for all). LPS administration decreased plasma concentrations of L -arginine from 66 µmol/l [95% CI (confidence interval): 56, 88] at baseline to 48 µmol/l (CI: 40, 60) after 3.5 h ( P <0.02), but did not affect ADMA and SDMA concentrations. Consequently, the L -arginine/ADMA ratio declined significantly from a median of 159 (CI: 137, 193) to 135 (CI: 103, 146); a decrease of 25 (CI: -68, -13; P <0.02). L -Arginine, ADMA, SDMA and the L -arginine/ADMA ratio remained constant over time in controls. Acute inflammation reduces the L -arginine/ADMA ratio which could contribute to impaired vascular function.

Studies in animals and humans indicate a pivotal role for adhesion molecules (AMs) in the pathogenesis of atherosclerosis. Whereas an association between hypercholesterolaemia and AM expression has been suggested, it is unclear whether lowering cholesterol decreases AM expression and release. We compared the effects of a 3-month treatment with standard doses of three different statins (atorvastatin, simvastatin and pravastatin) on plasma levels of circulating AM (cAM) in 75 hypercholesterolaemic patients in a randomized clinical trial. Plasma levels of circulating (c)E-selectin, circulating intercellular adhesion molecule-1 (cICAM-1) and circulating vascular cell adhesion molecule-1 (cVCAM-1) were measured before and after 3 months of therapy. None of the statins lowered plasma cAM levels and pooled analyses of all patients showed a 1.7% [95% confidence interval (CI), -1.4–4.9%] increase in cE-selectin, a 2.1% (95% CI, -0.2–4.4%) increase in cICAM-1, and a 2.7% (95% CI, -0.6–6.1%) increase in cVCAM-1 levels. cAM levels did not decrease, even in patients with a >50% decrease ( n = 19) in low-density lipoprotein cholesterol levels. This study provides strong evidence that 3 months of therapy with three different statins does not decrease cAM levels, despite normalization of cholesterol levels, and a minor decrease in C-reactive protein levels in patients with moderate hypercholesterolaemia.