Nitric oxide and endothelin after lipid apheresis - a pilot study.

OBJECTIVE: Patients with the heterozygous form of familial hypercholesterolemia (FH) display an early onset of atherosclerosis due to disturbed vascular-endothelial function. Whether the improvements of endothelial function after lipid apheresis are mediated by increased NO-production or by an altered turnover of vasoconstrictors such as ET-1 is still unknown. This was the onset of the present study. METHODS: Patients with FH and advanced atherosclerosis receiving regular LDL apheresis at 1 to 3 weeks were recruited. Lipids, L-arginine (L-Arg), L-hydroxyarginine (NHA), L-citrulline as well as big endothelin (Big-ET) and endothelin (ET-1) were measured after DALI, HELP and TheraSorb apheresis. RESULTS: 17 patients with severe FH aged 55.6 years (mean) received a total of 30 treatments. TC, LDL-C, HDL-C, TG and TC / HDL-C ratio were reduced (55, 70, 9, 48, and 52%; p<0.01) with no differences between apheresis systems. L-Arg was reduced after apheresis (HELP -18.0%, DALI -26.5%; Therasorb -7.6%) and returned to baseline after 2 h. Big-ET (p<0.01) and ET-1 were found to be increased directly and 2 hours after apheresis with HELP while transiently decreasing with DALI and Therasorb. CONCLUSION: Improvement of endothelial function after apheresis seems to have multifaceted causes. The further elucidation of the interrelationship between endothelial dysfunction and restricted NO synthesis, as addressed in this study by measuring L-NHA, L-Arg, L-Cit, ET-1 and Big-ET will be necessary in the future.

Reduced insulin secretion and content in VEGF-a deficient mouse pancreatic islets.

Mice, deficient for vascular endothelial growth factor VEGF-A in pancreatic islets, have reduced insulin gene expression levels and an impaired glucose tolerance. Here, we investigated whether VEGF-A was required for physiological glucose-stimulated insulin secretion and insulin content. We performed in situ pancreas perfusions and islet perifusions on mice lacking VEGF-A in the pancreatic epithelium in order to study their ability to secrete insulin in response to glucose. We identified insulin secretion defects in the pancreata of VEGF-A deficient mice, including a delayed and blunted response to glucose. Islet perifusion experiments revealed a missing first phase and weaker second phase of insulin secretion, in two of three VEGF-A deficient mice. On average, insulin content in VEGF-A deficient islets was significantly reduced when compared with control islets. We conclude that VEGF-A is required in pancreatic islets for normal glucose-stimulated insulin secretion and physiological insulin content. Thus, VEGF-A is a key factor for pancreatic islet function.

Heparin-induced Extracorporal LDL precipitation (H.E.L.P) in diabetic foot syndrome - preventive and regenerative potential?

Peripheral arterial disease is more aggressive in concomitant diabetes posing an increased risk for critical limb ischemia and subsequent limb loss. The majority of therapies available are not effective to prevent amputation in patients with severe disease. The current observational study reports the effect of the heparin-induced extracorporal LDL-precipitation (H.E.L.P.) as a novel therapeutic approach in patients with severe diabetic foot syndrome. Seventeen diabetic patients with septic foot lesions recruited from the diabetic outpatient clinic underwent H.E.L.P. apheresis regularly until fibrinogen levels were stabilized at 3 g/l or infection was controllable as evidenced by alleviation of necrosis. Patients were subsequently followed up for 2 to 73 months. Fibrinogen levels were reduced by 68% after H.E.L.P. treatment. No severe complications were noted. Necrosis could be confined in sixteen patients. Minor amputations were indicated in twelve patients. Three patients underwent major amputations of the lower limb and two patients received surgical reconstruction. In conclusion, H.E.L.P. apheresis may offer an alternative therapeutic option to diabetic patients with critically ischemic feet and appears to have a beneficial major/minor amputation ratio.