Long-term follow-up of circulating oxidative stress markers in patients undergoing lipoprotein apheresis by Direct Adsorption of Lipids (DALI).

Objective: Beyond its well-established efficacy in lowering atherogenic lipids and lipoproteins, DALI (Direct Adsorption of Lipids) apheresis has been shown to have acute anti-inflammatory and endothelium-protective effects. In the present study, we investigated long-term effects of DALI procedures on circulating oxidative stress markers.

Methods: Thirteen patients involved in the study underwent regular DALI apheresis for nearly two years.

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Increased plasma aldosterone concentration is significantly associated with dementia, which is accentuated by diabetes mellitus (DM). Angiotensin II (AngII) deteriorates cognitive function through neuronal degradation. Lipoproteins, a major source of cholesterol for aldosterone biosynthesis, undergo glycoxidative modifications in the presence of hyperglycemia.

Detection of Independent Associations of Plasma Lipidomic Parameters with Insulin Sensitivity Indices Using Data Mining Methodology.

Objective: Glucolipotoxicity is a major pathophysiological mechanism in the development of insulin resistance and type 2 diabetes mellitus (T2D). We aimed to detect subtle changes in the circulating lipid profile by shotgun lipidomics analyses and to associate them with four different insulin sensitivity indices.

Methods: The cross-sectional study comprised 90 men with a broad range of insulin sensitivity including normal glucose tolerance (NGT, n = 33), impaired glucose tolerance (IGT, n = 32) and newly detected T2D (n = 25).

Association between systemic oxidative stress and insulin resistance/sensitivity indices - the PREDIAS study.

Objective: Systemic oxidative stress has been causally related to insulin resistance and the subsequent development of type 2 diabetes mellitus (T2D). We investigated associations between circulating oxidative stress markers and different surrogate indexes of insulin sensitivity/resistance.

Patients: Cross-sectional data were obtained from 1183 subjects with normal glucose tolerance (NGT), 280 subjects with impaired glucose tolerance (IGT) and 69 newly detected T2D individuals entering the PREDIAS (prevention of diabetes) study.

Increasing plasma lysophosphatidylcholine levels in patients with regular dextran sulfate lipoprotein apheresis.

Objectives: Previously we found a highly significant increase of phosphatidylethanolamines (PE) in response to acute lipoprotein apheresis (LA) with whole blood dextran sulfate adsorption (DSA) in contrast to the overall tendency of reduction of lipid metabolites of all lipid classes in post-apheresis plasma. Therefore, the aim of the present study was to analyze long-term modifications of the plasma lipidomic profile in patients with repeated DSA apheresis.

Methods: Nine patients weekly treated with DSA were followed for 40 weeks.

Long-term therapeutic efficacy of lipoprotein apheresis on circulating oxidative stress parameters--A comparison of two different apheresis techniques.

Background: A chronic lipoprotein apheresis therapy leads to an expressed reduction in the incidence of cardiovascular events in high-risk patients. In addition to the elimination of atherogenic lipoproteins such as LDL and lipoprotein(a), an antioxidative effect of lipoprotein apheresis has been suspected.

Objectives And Methods: We investigated long-term biochemical effects in sixteen patients undergoing lipoprotein apheresis - lipid filtration (LF, n = 7) or dextran sulfate adsorption (DSA, n = 9).

Stimulation of phagocyte adhesion to endothelial cells by modified VLDL and HDL requires scavenger receptor BI.

Hyperglycemia- and oxidative stress-induced modification of circulating lipoproteins is being increasingly recognized as an important pathogenetic factor for diabetic cardiovascular damages. This study was designed to investigate the impact of modified very low-density lipoprotein and high-density lipoprotein on phagocyte adhesion to endothelial cells and the involvement of scavenger receptor class B type 1 (SR-BI) in this process. Native lipoproteins were isolated by density gradient ultracentrifugation and in vitro glycoxidative or oxidative modification was performed in the presence of glucose or sodium hypochlorite, respectively.

Modified high-density lipoprotein modulates aldosterone release through scavenger receptors via extra cellular signal-regulated kinase and Janus kinase-dependent pathways.

Patients with type 2 diabetes (T2D) manifest significant abnormalities in lipoprotein structure and function. The deleterious impact of oxidative and glycoxidative modifications on HDL-mediated atheroprotective, antiinflammatory, and antioxidative phenomena has been well established. However, the biological effects of modified HDL on adrenal steroidogenesis-which could reveal a pathophysiological link to the overactivity of the renin-angiotensin-aldosterone system and its adverse cardiovascular consequences often observed in T2D-are not well delineated.

Very-low-density lipoprotein mediates transcriptional regulation of aldosterone synthase in human adrenocortical cells through multiple signaling pathways.

Diabetic dyslipidemia is characterized by increased circulatory very-low-density lipoprotein (VLDL) levels. Aldosterone, apart from its role in fluid and electrolyte homeostasis, has also been implicated in insulin resistance and myocardial fibrosis. The impact of VLDL as a potential risk factor for aldosterone-mediated cardiovascular injury in diabetes mellitus, however, remains to be investigated.

The osteoclast-associated receptor (OSCAR) is a novel receptor regulated by oxidized low-density lipoprotein in human endothelial cells.

Cross talks between the vascular and immune system play a critical role in vascular diseases, in particular in atherosclerosis. The osteoclast-associated receptor (OSCAR) is a regulator of osteoclast differentiation and dendritic cell maturation. Whether OSCAR plays a role in vascular biology and has an impact on atherogenic processes provoked by proinflammatory stimuli is yet unknown.

Modulation of adrenal aldosterone release by oxidative modification of low-density lipoprotein.

Background: Serum aldosterone is a causative factor for various metabolic and cardiovascular disorders. Low-density lipoprotein (LDL) is a major cholesterol source for aldosterone steroidogenesis; however, the effect of oxidative modification of LDL on aldosterone release is not known. We studied the effect of hypochlorite-oxidized LDL (oxLDL) on adrenal aldosterone secretion.

Type 2 diabetes in octogenarians is associated with decreased low molecular weight adiponectin.

Background: Adiponectin circulates in the blood in three different multimer isoforms, of which the high molecular weight form (HMW) is presumed to mediate insulin sensitivity. We examined whether adiponectin oligomer distribution is associated with aging and type 2 diabetes (T2D) in octogenarians without characteristic features of metabolic syndrome.

Methods: The study included 154 octogenarians (58 men, 96 women), 24 normoglycemic middle-aged controls (11 men, 13 women; mean age 44 years), and 33 middle-aged individuals (14 men, 19 women; mean age 55 years) with T2D.

Beyond lowering circulating LDL: apheresis-induced changes of systemic oxidative stress markers by four different techniques.

Objective And Methods: Dyslipidemia and oxidative stress are causally related to atherogenesis and cardiovascular disease. We assessed acute changes of systemic oxidative stress biomarkers in thirty-two patients undergoing regular apheresis using four different techniques: heparin-induced extracorporeal LDL precipitation (HELP), direct adsorption of lipoproteins (DALI), lipidfiltration (LF), and immunoadsorption of lipoproteins (IA).

Results: All apheresis procedures were similarly effective in lowering LDL cholesterol (-2.

Endothelial factors mediate aldosterone release via PKA-independent pathways.

Aldosterone synthesis is primarily regulated by angiotensin II and potassium ions. In addition, endothelial cell-secreted factors have been shown to regulate mineralocorticoid release. We analyzed the pathways that mediate endothelial cell-factor-induced aldosterone release from adrenocortical cells, NCI-H295R using endothelial cell-conditioned medium (ECM).

Prediabetic and diabetic in vivo modification of circulating low-density lipoprotein attenuates its stimulatory effect on adrenal aldosterone and cortisol secretion.

Modification of low-density lipoprotein (LDL) and abnormal aldosterone and cortisol metabolism have been implicated in the pathogenesis of type 2 diabetes (DM2) and diabetic vascular disease. Since LDL serves as a major cholesterol source for adrenal steroidogenesis, we investigated whether LDL modification in prediabetic and diabetic subjects influences adrenocortical aldosterone and cortisol release. LDL was isolated from 30 subjects with normal glucose tolerance (NGT-LDL), 30 subjects with impaired glucose tolerance (IGT-LDL), and 26 patients with DM2 (DM2-LDL).

Comparison of different LDL apheresis methods.

This article presents the generally accepted indications for LDL apheresis treatment. The available LDL apheresis methods differ with respect to acute relative reductions of LDL cholesterol; mean values after the LDL apheresis treatments are not different. Serum triglycerides, HDL-cholesterol, and lipoprotein(a) are also acutely reduced.

Endothelial cell-mediated regulation of aldosterone release from human adrenocortical cells.

Endothelial cells play an important role in the development and functioning of endocrine tissue and endothelial cell-derived factors have been shown to regulate mineralocorticoid release in bovine adrenal cells. In the present study, we analysed the role of human endothelial cells in the synthesis and release of aldosterone from adrenocortical cells (NCI-H295R). Endothelial cell-induced aldosterone release was rapid and lasted as a long-term effect over a period of 48 h.

[Intravenous oxygen therapy increases the activity of the antioxidative and antiatherogenic serum enzyme paraoxonase 1].

Background: Intravenous oxygen infusions have been introduced in complementary medicine for treatment of atherosclerosis and inflammatory diseases. As atherosclerosis and inflammation are causally related to oxidative stress and as intravenous supply with oxygen causes oxidative stress, it was suggested that the clinical success of intravenous oxygen therapy is biochemically based on an enhancement of endogenous antioxidative mechanisms. The anti-atherogenic enzyme paraoxonase-1 (PON1) is is part of this system.

Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population.

Objective: Human urate transporter 1 (hURAT1) is a member of the organic anion transporter family (SLC22A12) that mainly regulates tubular urate reabsorption. Loss-of-function mutations result in idiopathic hypouricemia. The present case-control study was designed to analyze whether hURAT1 might also be a candidate gene for hyperuricemia with primary reduced renal urate excretion.

Association of chondromodulin-II Val58Ile polymorphism with radiographic joint destruction in rheumatoid arthritis.

Objective: Chondromodulin-II (ChM-II) is a cartilage-derived protein involved in cartilage and bone repair. A study of Japanese patients with rheumatoid arthritis (RA) implicated an association between a 172G --> A (Val58Ile) polymorphism and radiographic damage. We analyzed ChM-II for polymorphisms and investigated the association with radiographically assessed joint destruction in German patients with RA.

Hypochlorite-oxidized low-density lipoprotein upregulates CD36 and PPARgamma mRNA expression and modulates SR-BI gene expression in murine macrophages.

The uptake of oxidized low-density lipoprotein (oxLDL) by scavenger receptors of macrophages with resulting foam cell formation is considered a critical event in atherogenesis. Since hypochlorite-oxidized LDL (HOCl-LDL) has been shown to be recognized by macrophages and evidence was provided that HOCl-LDL is internalized via class B scavenger receptors CD36 and SR-BI, the regulatory relationships between CD36, SR-BI, and the nuclear transcription factor PPARgamma in murine macrophages (RAW 264.7) on exposure to HOCl-LDL were examined.

The protective effects of HDL and its constituents against neutrophil respiratory burst activation by hypochlorite-oxidized LDL.

Hypochlorite-oxidized low-density lipoprotein (oxLDL) possesses a substantial proinflammatory potential by modulating respiratory burst activities of polymorphonuclear neutrophils (PMN). As evaluated by luminol-amplified chemiluminescence (CL) incubation of 10(6) PMN/ml with 70 nM oxLDL was followed by substantial induction of neutrophil oxidant (ROS) generation. We evaluated the inhibitory capacity of high-density lipoprotein (HDL) and its lipid and protein constituents against the activating effects of oxLDL.

The pivotal role of scavenger receptor CD36 and phagocyte-derived oxidants in oxidized low density lipoprotein-induced adhesion to endothelial cells.

Adhesion of phagocytes to endothelial cells constitutes a crucial step in atherogenesis. Oxidized low density lipoproteins (LDL) are supposed to facilitate the adhesion process. We investigated the molecular mechanisms by which mildly and extensively hypochlorite-oxidized LDL force adhesion of murine macrophages and human neutrophils to human umbilical venous endothelial cells.