Institute For Klinische Biochemie Und Pathobiochemie

Düsseldorf, Germany

Institute For Klinische Biochemie Und Pathobiochemie

Düsseldorf, Germany

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Grandoch M.,Heinrich Heine University Düsseldorf | Grandoch M.,Cardiovascular Research Institute Dusseldorf CARID | Feldmann K.,Heinrich Heine University Düsseldorf | Feldmann K.,Cardiovascular Research Institute Dusseldorf CARID | And 23 more authors.
Circulation Research | Year: 2015

Rationale: Lymphotoxin β receptor (LTbR) regulates immune cell trafficking and communication in inflammatory diseases. However, the role of LTbR in atherosclerosis is still unclear. Objective: The aim of this study was to elucidate the role of LTbR in atherosclerosis. Methods and Results: After 15 weeks of feeding a Western-type diet, mice double-deficient in apolipoprotein E and LTbR (apoE-/-/LTbR-/-) exhibited lower aortic plaque burden than did apoE-/- littermates. Macrophage content at the aortic root and in the aorta was reduced, as determined by immunohistochemistry and flow cytometry. In line with a decrease in plaque inflammation, chemokine (C-C motif) ligand 5 (Ccl5) and other chemokines were transcriptionally downregulated in aortic tissue from apoE-/-/LTbR-/- mice. Moreover, bone marrow chimeras demonstrated that LTbR deficiency in hematopoietic cells mediated the atheroprotection. Furthermore, during atheroprogression, apoE-/- mice exhibited increased concentrations of cytokines, for example, Ccl5, whereas apoE-/-/LTbR-/- mice did not. Despite this decreased plaque macrophage content, flow cytometric analysis showed that the numbers of circulating lymphocyte antigen 6C (Ly6C)low monocytes were markedly elevated in apoE-/-/LTbR-/- mice. The influx of these cells into atherosclerotic lesions was significantly reduced, whereas apoptosis and macrophage proliferation in atherosclerotic lesions were unaffected. Gene array analysis pointed to chemokine (C-C motif) receptor 5 as the most regulated pathway in isolated CD115+ cells in apoE-/-/LTbR-/- mice. Furthermore, stimulating monocytes from apoE-/- mice with agonistic anti-LTbR antibody or the natural ligand lymphotoxin-α1β2, increased Ccl5 mRNA expression. Conclusions: These findings suggest that LTbR plays a role in macrophage-driven inflammation in atherosclerotic lesions, probably by augmenting the Ccl5-mediated recruitment of monocytes. © 2015 American Heart Association, Inc.


Panza G.,Heinrich Heine University Düsseldorf | Luers L.,Heinrich Heine University Düsseldorf | Stohr J.,Heinrich Heine University Düsseldorf | Nagel-Steger L.,Heinrich Heine University Düsseldorf | And 6 more authors.
PLoS ONE | Year: 2010

Prion diseases like Creutzfeldt-Jakob disease in humans, Scrapie in sheep or bovine spongiform encephalopathy are fatal neurodegenerative diseases, which can be of sporadic, genetic, or infectious origin. Prion diseases are transmissible between different species, however, with a variable species barrier. The key event of prion amplification is the conversion of the cellular isoform of the prion protein (PrPC) into the pathogenic isoform (PrPSc). We developed a sodiumdodecylsulfatebased PrP conversion system that induces amyloid fibril formation from soluble α-helical structured recombinant PrP (recPrP). This approach was extended applying pre-purified PrPSc as seeds which accelerate fibrillization of recPrP. In the present study we investigated the interspecies coherence of prion disease. Therefore we used PrPSc from different species like Syrian hamster, cattle, mouse and sheep and seeded fibrillization of recPrP from the same or other species to mimic in vitro the natural species barrier. We could show that the in vitro system of seeded fibrillization is in accordance with what is known from the naturally occurring species barriers. © 2010 Panza et al.


Luers L.,Heinrich Heine University Düsseldorf | Panza G.,Heinrich Heine University Düsseldorf | Henke F.,Jülich Research Center | Agyenim T.,Heinrich Heine University Düsseldorf | And 5 more authors.
Rejuvenation Research | Year: 2010

Protein aggregation occurs in many age-related neurodegenerative diseases, where it can lead to deposits of naturally occurring proteins in the brain. In case of Creutzfeldt-Jakob disease (CJD), these deposits consist of prion protein (PrP). CJD has three etiologies: spontaneous, genetic, or caused by infection. A polymorphism within the PrP gene is associated with susceptibility of infection. The main event in prion diseases is the conversion of PrP from its naturally occurring isoform to its disease-associated isoform. Here, we present the adaption of a previously reported in vitro conversion system based on hamster recombinant PrP to analyze amyloid fibril formation of human recombinant PrP. We further compare the aggregation characteristics of the human PrP according to the polymorphism variants M129 and V129. © 2010 Mary Ann Liebert, Inc.


Lapauw B.,Ghent University | Ouwens M.,Institute For Klinische Biochemie Und Pathobiochemie | 'T Hart L.M.,Leiden University | Wuyts B.,Ghent University | And 4 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - To evaluate metabolic effects of sex steroids in nonfasting and fasting conditions, independent from changes in body composition. RESEARCH DESIGN AND METHODS - A randomized clinical trial was performed to create contrasting sex steroid levels in healthy young men: by letrozole (aromatase inhibitor) to lower estradiol (E 2) and increase testosterone (group T, n = 10) versus letrozole plus E 2 patches to lower T and raise E 2 (group E, n = 10). Mixed meals and hyperinsulinemic-euglycemic clamps were performed before and after a 1-week treatment period. RESULTS - Following intervention, the postprandial triglyceride response displayed a diverging response with a decline in group T and an increase in group E; the postprandial glucose-dependent insulinotropic polypeptide (GIP) response increased in group T. Insulin sensitivity increased in group T but remained unaltered in group E. CONCLUSIONS - In healthy young men, short-term changes in sex steroids affect postprandial triglyceride and GIP response and insulin sensitivity. © 2010 by the American Diabetes Association.


Vormbrock I.,Heinrich Heine University Düsseldorf | Kaber G.,Heinrich Heine University Düsseldorf | Hartwig S.,Institute For Klinische Biochemie Und Pathobiochemie | Eckel J.,Institute For Klinische Biochemie Und Pathobiochemie | And 2 more authors.
Archives of Physiology and Biochemistry | Year: 2010

Over the last decade surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) has evolved as a versatile tool in the field of proteomic research. Although the chromatographic matrices on the currently provided SELDI affinity arrays allow efficient on-chip protein enrichment, it can be advantageous to combine SELDI with additional sample pre-fractionation steps. In this study, we demonstrate the potential of combining hydroxyapatite-based phosphoprotein enrichment with SELDI-TOF MS analysis. A straightforward method for the enrichment of phosphoproteins on ceramic hydroxyapatite was developed using fluorescently-labelled model proteins. Hydroxyapatite-based pre-fractionation of proteins derived from cell lysates was performed. SELDI-TOF MS analysis of the pre-fractionation eluate confirmed a considerable reduction of sample complexity and an enhancement of selected protein signals. © 2010 Informa UK, Ltd.


Muller-Wieland D.,Institute For Diabetologische Versorgungsforschung | Knebel B.,Institute For Klinische Biochemie Und Pathobiochemie | Haas J.,Institute For Diabetologische Versorgungsforschung | Merkel M.,Institute For Diabetologische Versorgungsforschung | Kotzka J.,Institute For Klinische Biochemie Und Pathobiochemie
Herz | Year: 2010

The metabolic syndrome is usually associated with insulin resistance and visceral fat distribution, which appear to play a direct role in the development of clinical criteria of metabolic syndrome, like elevation of arterial blood pressure and dyslipidemia. In this review, the authors will first introduce the concept, that insulin resistance and increased visceral adipose tissue are also regularly associated with an abnormal or ectopic accumulation of lipids in nonadipocytes, like steatosis hepatis. Then, they will provide some evidence that epicardial fat can be associated with insulin resistance in a similar fashion as visceral intraabdominal fat. Furthermore, epicardial fat might directly affect the vessels and function of the heart. Accordingly, ectopic accumulation of fat within cardiac muscle cells can impair their function and possibly be related to heart failure. These new relations between obesity, fat distribution and cardiac function might help to identify and treat individuals at risk earlier and more appropriately. © 2010 Urban & Vogel.

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