Hyperlipidemias: Wieland E

Schettler V, Wieland E. · Nephrologisches Zentrum Göttingen, Göttingen. · Dtsch Med Wochenschr. · Pubmed #17342636 No free full text.

Abstract: LDL apheresis is a safe and very effective extracorporeal treatment of refractory hypercholesterolemia. LDL cholesterol levels can be reduced with this procedure by more than 60%. C-reactive protein (CRP) is a known marker of inflammation in atherosclerosis. Interestingly CRP can be effectively removed by a single LDL apheresis, but further studies are needed to substantiate the effect of extracorporeal reduction of CRP on the progression of atherosclerosis. However, adhesion molecules and activities of inflammatory cells were also found to be reduced after a single LDL apheresis. The biochemical composition of newly formed LDL particles after apheresis is altered: LDL particles isolated after LDL apheresis had an increased resistance to oxidative stress in vitro. In addition, antioxidants are not depleted by LDL apheresis. The extracorporal method itself does not have a negative impact on the oxidative/antioxidative balance. A recent investigation showed that LDL-cholesterol had a more pronounced effect on blood rheology than fibrinogen. This observation may explain why a single LDL apheresis leads to better myocardial perfusion, as demonstrated by PET in patients with hypercholesterolemia. These additional effects have so far only been known with statins. Further investigations are needed to substantiate the observed potentially beneficial effects of LDLapheresis beyond its effect of lowering LDL.

Schettler V, Methe H, Staschinsky D, Schuff-Werner P, Müller GA, Wieland E. · Department of Nephrology and Rheumatology, Georg-August-University, Göttingen, Germany. · Ther Apher. · Pubmed #10427619 No free full text.

Abstract: Low density lipoprotein (LDL) apheresis is a safe procedure to treat severe hypercholesterolemia in patients with chronic heart disease (CHD). However, both hypercholesterolemia and extracorporeal treatment have been associated with oxidative stress. Even though LDL lowering has been proven to reduce CHD, the oxidative modification of LDL has been suggested to render these lipoproteins more atherogenic. It is therefore important to know whether LDL apheresis is safe with respect to oxidative stress including LDL oxidation. The contact of living cells such as leukocytes with artificial surfaces during extracorporeal treatment induces the liberation of various chemokines and cytokines as well as oxygen-derived radicals also known as respiratory burst. These effects justify the consideration of leukocyte activation resulting from extracorporeal treatment as an inflammatory reaction. In extracorporeal circuits such as those used for hemodialysis, the release of oxygen radicals has been shown and depends on the fiber material used in the dialyzer membranes. Reactive oxygen radicals can interact with different cell components such as carbohydrates, DNA, proteins, and lipids. Antioxidants in the form of low molecular weight molecules such as glutathione or radical scavenging enzymes such as superoxide dismutase offer protection against the damaging effects of prooxidants. The disturbed balance between prooxidants and antioxidants is considered as oxidative stress. Therefore, either an increase in oxygen radical formation or a decrease of antioxidants will lead to oxidative stress. During LDL apheresis, a decrease of low molecular weight antioxidants has been reported. In contrast, we have observed an increase in plasma glutathione concentrations but no severe reduction in the activity of antioxidant enzymes in plasma, red cells, or granulocytes, which may explain the lack of plasma lipid peroxidation shown during this kind of extracorporeal treatment. In addition, LDL isolated at the end of apheresis procedures are more resistant to oxidation. These findings suggest that LDL apheresis is safe with respect to radical mediated injury.

Schettler V, Krontal J, Scheel A, Wieland E. · Department of Nephrology and Rheumatology, Georg-August University, Göttingen, Germany. · Eur J Clin Invest. · Pubmed #12588287 No free full text.

Abstract: BACKGROUND: Lipid apheresis (LA) treatment has been suggested to cause oxidative stress. Defense against oxygen-radical-mediated damage is provided by nonenzymatic and enzymatic antioxidants. In the present investigation we have investigated whether gene expression of free radical scavenging enzymes (FRSE) is affected in leukocytes of patients undergoing LDL-apheresis. MATERIALS AND METHODS: For this purpose cellular glutathione peroxidase (GPx-1), phospholipid glutathione peroxidase (GPx-4), glutathione reductase (GSSG-R), glutathione synthetase (GSH-S), Cu/Zn-superoxide dismutase (SOD-1) and catalase (CAT) mRNA expression were followed at the start (SA) and immediately after (EA) LA treatment (n = 25). Gene expression was determined by quantitative RT-PCR with the LightCycler(R) instrument (Roche Diagnostics, Mannheim, Germany) and transcription elongation factor-2 as reference gene. RESULTS: The expression of GPx-1, GPx-4, GSSG-R, GSH-S, SOD-1, CAT mRNA was not affected by a single LA treatment. Free radical scavenging enzymes mRNAs were significantly (P < 0.05) increased in the LA patients (GPx-1: 2.00 +/- 1.37; GPx-4: 0.52 +/- 0.46; GSSG-R: 0.07 +/- 0.03; GSH-S: 0.04 +/- 0.03; SOD-1: 1.12 +/- 0.74; CAT: 0.15 +/- 0.07) when compared with 26 healthy blood donors (GPx-1: 1.1 +/- 0.6; GPx-4: 0.35 +/- 0.19; GSSG-R: 0.02 +/- 0.01; GSH-S: 0.03 +/- 0.01; SOD-1: 0.16 +/- 0.08; CAT: 0.09 +/- 0.05; mean +/- SD). CONCLUSIONS: These results show that the LA procedure does not acutely affect the antioxidant defense system on the gene level but suggests that the chronic stress resulting from hyperlipidaemia and/or LA may cause FRSE gene induction.