Clinical study of plasma lipocalin-2 and endothelial function

Abstract

Background Recent animal studies suggested that lipocalin-2 plays a key role in the development of hypertension, atherosclerosis and endothelial dysfunction. Lipocalin-2 knockout mice are resistant to the harmful effects of high fat diet and do not develop hypertension or atherosclerosis. We therefore hypothesised that lipocalin-2 is also related to endothelial function in man. Methods We measured plasma lipocalin-2 concentration and brachial artery flow-mediated dilatation (FMD) in 245 subjects (201 men, 44 women; mean age±SD, 68±9 y), of whom 151 had hypertension, 80 had diabetes mellitus and 240 were on lipid lowering therapy. Lipocalin-2 was measured using a highly-specific ELISA, with intra- and interassay coefficients of variation of 3.8-6.0% and 3.1–5.2% respectively. Brachial artery diameter and flow velocity were measured using a 7.5MHz ultrasound probe. Scans were taken at baseline, 5 minutes after tourniquet inflation and after sublingual glyceryl trinitrate spray. The percentage change in brachial artery diameter following reactive hyperaemia was calculated. The coefficient of variation of FMD determination was 5%. Results The median (IQR) plasma lipocalin-2 concentration was 50 (29-75) ng/mL. There was no sex difference. Plasma lipocalin-2 level correlated with serum creatinine (ρ=0.23, p<0.001) but not FMD (ρ=0.005, p=0.94). Instead, FMD decreased with age (ρ=-0.14, p=0.03). It is also lower in individuals with diabetes (p=0.044). Conclusions Endothelial function decreases with age and diabetes, but is unrelated to plasma lipocalin-2 level. This suggests that plasma lipocalin-2 level is not a major determinant of endothelial function. However, plasma lipocalin-2 is a marker for renal dysfunction.