de Karina Leeuw

Skin autofluorescence is increased in systemic lupus erythematosus but is not reflected by elevated plasma levels of advanced glycation endproducts

OBJECTIVES To examine whether skin advanced glycation endproducts (AGEs) accumulation, plasma levels of AGEs-N(epsilon)-carboxymethyllysine (CML) and N(epsilon)-carboxyethyllysine (CEL)-and serum levels of soluble receptor for AGEs (sRAGE) are elevated in SLE patients compared with controls, and whether these parameters are related to disease activity and endothelial cell (EC) activation. METHODS Ten SLE patients (9 women, age 34 +/- 13 yrs, mean +/- s.d.) and 10 age- and sex-matched controls were included. Patients were analysed during inactive as well as active disease. Skin AGE accumulation was estimated using ultraviolet-A (UV-A) light for measurement of autofluorescence obtained by Excitation-Emission matrix Scanner (AF-EEMS). Levels of CML and CEL were determined by tandem mass spectrometry. Levels of sRAGE and of soluble vascular cell adhesion molecule-1 (sVCAM-1) were determined by ELISAs. RESULTS Skin AF-EEMS was increased in SLE patients compared with controls (P < 0.05). Levels of CML and CEL were comparable between patients and controls and were not influenced by disease activity. sRAGE and sVCAM-1 levels were higher in quiescent SLE patients compared with controls (P < 0.05) and increased further during active disease (P < 0.05). In patients with quiescent disease and controls, sRAGE levels correlated to sVCAM-1 levels (r = 0.579, P = 0.007). CONCLUSIONS Skin AGEs and levels of sRAGE and sVCAM-1 were elevated in SLE patients, whereas levels of CML and CEL were comparable with controls. As sRAGE even further increased during endothelial activation, it might be hypothesized that sRAGE acts as a decoy receptor. Why this proposed mechanism is insufficient to prevent increased AGE accumulation in the skin of SLE patients has to be established.

Vascular responsiveness in the microcirculation of patients with systemic lupus erythematosus is not impaired

As endothelial dysfunction is one of the earliest signs of atherosclerosis, which is accelerated in systemic lupus erythematosus (SLE), we assessed whether vascular responses of the cutaneous microcirculation are disturbed in SLE patients and influenced by Raynaud’s phenomenon (RP). Laser Doppler fluxmetry (LDF) was used in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), an endothelium-dependent and endothelium-independent vasodilator respectively. 42 SLE patients with inactive disease, 12 of whom had RP and 19 age- and sex-matched controls were included. Furthermore, traditional and non-traditional risk factors for cardiovascular disease (CVD) were assessed, and markers of inflammation and endothelial activation were measured. Vascular responses of SLE patients without RP did not differ from controls. However, SLE patients with RP exhibited decreased vasodilatation compared with controls. SLE patients with RP also had longer arrival times of ACh and SNP than controls. Markers of inflammation and von Willebrand factor were increased in SLE patients. Smoking, the presence of SLE and RP were negatively associated with vascular responses in univariate analysis. In multivariate analyses, the only independent variable of vascular responses to ACh and SNP was the presence of RP. Despite signs of endothelial activation, SLE patients with inactive disease do not have altered vascular responses in the microcirculation compared with controls. In SLE patients with RP, cutaneous vascular responses to both ACh and SNP are impaired. Therefore, LDF of the microcirculation seems not to be the appropriate method to distinguish those SLE patients with an increased risk to develop CVD.

Skin capillary permeability in the diabetic foot with critical limb ischaemia: The effects of a phVEGF165 gene product

Aims   To measure capillary permeability, assessed by skin capillary sodium fluorescein (NaF) leakage, in patients with diabetes mellitus with critical limb ischaemia (DM‐CLI) and to compare the effects of vascular endothelial growth factor (VEGF) with those of placebo.