LIVIVO - Search results -

Search results

Result 1 - 10 of total 10

Search options

Article ; Online: Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation

Andrea Itano / Douglas Maslin / Kritika Ramani / Golbarg Mehraei / Nancy Carpenter / Taylor Cormack / Mahdi Saghari / Matthijs Moerland / Erin Troy / Will Caffry / Leslie Wardwell-Scott / Stuart Abel / Duncan McHale / Mark Bodmer

Frontiers in Medicine, Vol

2023 Volume 10

Abstract: IntroductionEDP1815 is a non-colonizing pharmaceutical preparation of a single stain of Prevotella histicola isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally ... ...

Abstract	IntroductionEDP1815 is a non-colonizing pharmaceutical preparation of a single stain of Prevotella histicola isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally delivered and gut restricted single strain of commensal bacteria can regulate inflammatory responses throughout the body.MethodsSupported by evidence for anti-inflammatory activity in three preclinical mouse models of Th1-, TH2-, and Th17-mediated inflammation, EDP1815 was tested clinically in three Phase 1b studies in patients with psoriasis, patients with atopic dermatitis, and healthy volunteers in a KLH skin challenge model.ResultsPreclinically, EDP1815 was efficacious in all three mouse models of inflammation, showing reduction in skin inflammation as well as related tissue cytokines. In the Phase 1b studies, EDP1815 was found to be well tolerated by participants, with a safety profile comparable to placebo, including no severe or consistent side-effects reported, and no evidence of immunosuppression with no opportunistic infection occurring in these studies. In psoriasis patients, signs of clinical efficacy were seen after 4 weeks of treatment, which continued beyond the treatment period in the higher-dose cohort. In atopic dermatitis patients, improvements were seen throughout the key physician-and patient-reported outcomes. In a healthy-volunteer study of a KLH-induced skin inflammatory response, consistent anti-inflammatory effects were seen in two cohorts through imaging-based measures of skin inflammation.DiscussionThis is the first report demonstrating clinical effects from targeting peripheral inflammation with a non-colonizing gut-restricted single strain of commensal bacteria, providing proof of concept for a new class of medicines. These clinical effects occur without systemic exposure of EDP1815 or modification of the resident gut microbiota, and with placebo-like safety and tolerability. The breadth of these clinical effects of EDP1815, combined with ...
Keywords	small intestine ; psoriasis ; atopic dermatitis ; Th1 ; Th2 ; Th17 ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Identification of peripheral vascular function measures and circulating biomarkers of mitochondrial function in patients with mitochondrial disease

Sebastiaan J. W. vanKraaij / Diana R. Pereira / Bastiaan Smal / Luciana Summo / Anne Konkel / Janine Lossie / Andreas Busjahn / Tom N. Grammatopoulos / Erica Klaassen / Robert Fischer / Wolf‐Hagen Schunck / Pim Gal / Matthijs Moerland

Clinical and Translational Science, Vol 16, Iss 7, Pp 1258-

2023 Volume 1271

Abstract: Abstract The development of pharmacological therapies for mitochondrial diseases is hampered by the lack of tissue‐level and circulating biomarkers reflecting effects of compounds on endothelial and mitochondrial function. This phase 0 study aimed to ... ...

Abstract	Abstract The development of pharmacological therapies for mitochondrial diseases is hampered by the lack of tissue‐level and circulating biomarkers reflecting effects of compounds on endothelial and mitochondrial function. This phase 0 study aimed to identify biomarkers differentiating between patients with mitochondrial disease and healthy volunteers (HVs). In this cross‐sectional case–control study, eight participants with mitochondrial disease and eight HVs matched on age, sex, and body mass index underwent study assessments consisting of blood collection for evaluation of plasma and serum biomarkers, mitochondrial function in peripheral blood mononuclear cells (PBMCs), and an array of imaging methods for assessment of (micro)circulation. Plasma biomarkers GDF‐15, IL‐6, NT‐proBNP, and cTNI were significantly elevated in patients compared to HVs, as were several clinical chemistry and hematology markers. No differences between groups were found for mitochondrial membrane potential, mitochondrial reactive oxygen production, oxygen consumption rate, or extracellular acidification rate in PBMCs. Imaging revealed significantly higher nicotinamide‐adenine‐dinucleotide‐hydrogen (NADH) content in skin as well as reduced passive leg movement‐induced hyperemia in patients. This study confirmed results of earlier studies regarding plasma biomarkers in mitochondrial disease and identified several imaging techniques that could detect functional differences at the tissue level between participants with mitochondrial disease and HVs. However, assays of mitochondrial function in PBMCs did not show differences between participants with mitochondrial disease and HVs, possibly reflecting compensatory mechanisms and heterogeneity in mutational load. In future clinical trials, using a mix of imaging and blood‐based biomarkers may be advisable, as well as combining these with an in vivo challenge to disturb homeostasis.
Keywords	Therapeutics. Pharmacology ; RM1-950 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The Effect of a 13-Valent Conjugate Pneumococcal Vaccine on Circulating Antibodies Against Oxidized LDL and Phosphorylcholine in Man, A Randomized Placebo-Controlled Clinical Trial

Hendrika W. Grievink / Pim Gal / Maria Ozsvar Kozma / Erica S. Klaassen / Johan Kuiper / Jacobus Burggraaf / Christoph J. Binder / Matthijs Moerland

Biology, Vol 9, Iss 345, p

2020 Volume 345

Abstract: In mice vaccination with Streptococcus pneumoniae results in an increase in anti-oxLDL IgM antibodies due to mimicry of anti-phosphorylcholine (present in the cell wall of S. pneumoniae ) and anti-oxLDL IgM. In this study we investigated the human ... ...

Abstract	In mice vaccination with Streptococcus pneumoniae results in an increase in anti-oxLDL IgM antibodies due to mimicry of anti-phosphorylcholine (present in the cell wall of S. pneumoniae ) and anti-oxLDL IgM. In this study we investigated the human translation of this molecular mimicry by vaccination against S. pneumoniae using the Prevenar-13 vaccine. Twenty-four healthy male volunteers were vaccinated with Prevenar-13, either three times, twice or once in a double-blind, placebo-controlled, randomized single center clinical study. Anti-pneumococcal wall, oxLDL and phosphorycholine antibody levels were measured at a fixed serum dilution, as well as circulating lipid levels over the course of 68 weeks. A significant increase in anti-oxLDL IgG and IgM was seen in the group receiving two doses six months apart compared to the placebo. However, these differences were not observed in the groups receiving a single dose, two doses one month apart, or three doses. This study shows that vaccination with Prevenar-13 does not result in robust anti-oxLDL IgM levels in humans. Further research would be required to test alternative pneumococcal-based vaccines, vaccination regimens or study populations, such as cardiovascular disease patients.
Keywords	cardiovascular disease ; vaccine ; clinical trials ; translational medicine ; atherosclerosis ; oxLDL ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Whole blood assay as a model for in vitro evaluation of inflammasome activation and subsequent caspase-mediated interleukin-1 beta release.

Thi Anh Thu Tran / Hendrika W Grievink / Katarzyna Lipinska / Cornelis Kluft / Jacobus Burggraaf / Matthijs Moerland / Dimitar Tasev / Karen E Malone

PLoS ONE, Vol 14, Iss 4, p e

2019 Volume 0214999

Abstract: Processing of pro-interleukin (IL)-1β and IL-18 is regulated by multiprotein complexes, known as inflammasomes. Inflammasome activation results in generation of bioactive IL-1β and IL-18, which can exert potent pro-inflammatory effects. Our aim was to ... ...

Abstract	Processing of pro-interleukin (IL)-1β and IL-18 is regulated by multiprotein complexes, known as inflammasomes. Inflammasome activation results in generation of bioactive IL-1β and IL-18, which can exert potent pro-inflammatory effects. Our aim was to develop a whole blood-based assay to study the inflammasome in vitro and that also can be used as an assay in clinical studies. We show whole blood is a suitable milieu to study inflammasome activation in primary human monocytes. We demonstrated that unprocessed human blood cells can be stimulated to activate the inflammasome by the addition of adenosine 5'-triphosphate (ATP) within a narrow timeframe following lipopolysaccharide (LPS) priming. Stimulation with LPS resulted in IL-1β release; however, addition of ATP is necessary for "full-blown" inflammasome stimulation resulting in high IL-1β and IL-18 release. Intracellular cytokine staining demonstrated monocytes are the major producers of IL-1β in human whole blood cultures, and this was associated with activation of caspase-1/4/5, as detected by a fluorescently labelled caspase-1/4/5 probe. By applying caspase inhibitors, we show that both the canonical inflammasome pathway (via caspase-1) as well as the non-canonical inflammasome pathway (via caspases-4 and 5) can be studied using this whole blood-based model.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll‐Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells

Hendrika W. Grievink / Silvana M. G. Jirka / Tess D. Woutman / Mascha Schoonakker / Robert Rissmann / Karen E. Malone / Gary Feiss / Matthijs Moerland

Clinical and Translational Science, Vol 13, Iss 5, Pp 891-

2020 Volume 895

Abstract: LL‐37 is a cationic antimicrobial peptide and the sole human member of cathelicidins. Besides its bactericidal properties, LL‐37 is known to have direct immunomodulatory effects, among which enhancement of antiviral responses via endosomal toll‐like ... ...

Abstract	LL‐37 is a cationic antimicrobial peptide and the sole human member of cathelicidins. Besides its bactericidal properties, LL‐37 is known to have direct immunomodulatory effects, among which enhancement of antiviral responses via endosomal toll‐like receptors (TLRs). Omiganan pentahydrochloride is a synthetic cationic peptide in clinical development. Previously, omiganan was primarily known for its direct bactericidal and antifungal properties. We investigated whether omiganan enhances endosomal TLR responses, similar to LL‐37. Human peripheral blood mononuclear cells were treated with endosomal TLR3, −7, −8, and −9 ligands in the presence of omiganan. Omiganan enhanced TLR‐mediated interferon‐α release. Subsequent experiments with TLR9 ligands showed that plasmacytoid dendritic cells were main contributors to omiganan‐enhanced IFN production. Based on this type I interferon‐enhancing effect, omiganan may qualify as potential treatment modality for virus‐driven diseases. The molecular mechanism by which omiganan enhances endosomal TLR responses remains to be elucidated.
Keywords	Therapeutics. Pharmacology ; RM1-950 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Omiganan Enhances Imiquimod‐Induced Inflammatory Responses in Skin of Healthy Volunteers

Tessa Niemeyer‐van der Kolk / Salma Assil / Thomas P. Buters / Melanie Rijsbergen / Erica S. Klaassen / Gary Feiss / Edwin Florencia / Errol P. Prens / Jacobus Burggraaf / Martijn B.A. vanDoorn / Robert Rissmann / Matthijs Moerland

Clinical and Translational Science, Vol 13, Iss 3, Pp 573-

2020 Volume 579

Abstract: Omiganan (OMN; a synthetic cationic peptide) and imiquimod (IMQ; a TLR7 agonist) have synergistic effects on interferon responses in vitro. The objective of this study was to translate this to a human model for proof‐of‐concept, and to explore the ... ...

Abstract	Omiganan (OMN; a synthetic cationic peptide) and imiquimod (IMQ; a TLR7 agonist) have synergistic effects on interferon responses in vitro. The objective of this study was to translate this to a human model for proof‐of‐concept, and to explore the potential of OMN add‐on treatment for viral skin diseases. Sixteen healthy volunteers received topical IMQ, OMN, or a combination of both for up to 4 days on tape‐stripped skin. Skin inflammation was quantified by laser speckle contrast imaging and 2D photography, and molecular and cellular responses were analyzed in biopsies. IMQ treatment induced an inflammatory response of the skin. Co‐treatment with OMN enhanced this inflammatory response to IMQ, with increases in perfusion (+17.1%; 95% confidence interval (CI) 5.6%–30%; P < 0.01) and erythema (+1.5; 95% CI 0.25%–2.83; P = 0.02). Interferon regulatory factor‐driven and NFκB‐driven responses following TLR7 stimulation were enhanced by OMN (increases in IL‐6, IL‐10, MXA, and IFNɣ), and more immune cell infiltration was observed (in particular CD4+, CD8+, and CD14+ cells). These findings are in line with the earlier mechanistic in vitro data, and support evaluation of imiquimod/OMN combination therapy in human papillomavirus‐induced skin diseases.
Keywords	Therapeutics. Pharmacology ; RM1-950 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Applying caspase-1 inhibitors for inflammasome assays in human whole blood

Lipinska, Katarzyna / Cornelis Kluft / Karen E. Malone / Matthijs Moerland

Journal of Immunological Methods. 2014 Sept., v. 411

2014

Abstract: Caspase-1 processes pro-IL-1Î² and pro-IL-18 into bioactive forms. Caspase-1 activity is regulated by a multiprotein complex known as an inflammasome. Multiple danger and damage associated signals drive inflammasome formation. Currently, evaluation of ... ...

Abstract	Caspase-1 processes pro-IL-1Î² and pro-IL-18 into bioactive forms. Caspase-1 activity is regulated by a multiprotein complex known as an inflammasome. Multiple danger and damage associated signals drive inflammasome formation. Currently, evaluation of inflammasome activity is of particular interest as its role in chronic and acute inflammatory pathologies becomes evident. Specific inhibitors are therefore required to evaluate the contributions of the inflammasome and IL-1Î² to these disease processes. While several inhibitors are available for caspase-1 blocking experiments, in this study we show effects of two commonly used caspase inhibitors: z-VAD-fmk and ac-YVAD-cmk on secretion of pro-inflammatory cytokines: IL-1Î², TNFÎ±, IL-8 and IL-6 in whole blood stimulated with LPS. We demonstrate ac-YVAD-cmk is a specific caspase-1 inhibitor resulting in pronounced decreases in IL-1Î² and less suppression of TNFÎ±, IL-6 and IL-8, while pan-caspase inhibitor, z-VAD-fmk, only weakly suppressed Il-1Î² while acting strongly on the other three cytokines. Furthermore, we demonstrated that simultaneous treatment of whole blood cultures with inhibitor and LPS fails to attenuate the IL-1Î² response. In contrast, pretreatment with inhibitors prior to LPS stimulation is required to achieve marked decreases in IL-1Î² production. Thereby also demonstrating IL-1Î² release by cells in whole blood culture stimulated with LPS is a rapid response. Thus studying inflammasome/caspase-1/IL-1Î² axis requires appropriate selection and application of inhibitors.
Keywords	blood ; caspase-1 ; humans ; inflammasomes ; interleukin-1beta ; interleukin-6 ; interleukin-8 ; secretion ; tumor necrosis factor-alpha
Language	English
Dates of publication	2014-09
Size	p. 66-69.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	120142-6
ISSN	1872-7905 ; 0022-1759
ISSN (online)	1872-7905
ISSN	0022-1759
DOI	10.1016/j.jim.2014.05.018
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Cologne/Königswinter

Zs.A 795: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Evaluation of the Effect of Aspirin on Platelet Aggregation

Annelieke C. Kruithof / Matthijs Moerland / Eleftheria A. Anastasopoulou / Pieter-Jan de Kam / Marieke L. de Kam / Jacobus Burggraaf

Journal of Biomedical Science and Engineering, Vol 08, Iss 01, Pp 40-

Methodological Recommendations for Aspirin-Drug Interaction Studies

2015 Volume 45

Abstract: Given the broad application of aspirin as antiplatelet drug, availability of standardized methodology to assess potential interaction with any co-medication on platelet aggregation is desired. We characterized the effect of aspirin (ASA) therapy on ... ...

Abstract	Given the broad application of aspirin as antiplatelet drug, availability of standardized methodology to assess potential interaction with any co-medication on platelet aggregation is desired. We characterized the effect of aspirin (ASA) therapy on collagen-induced platelet aggregation in whole blood to define such methodology. Collagen-induced platelet whole blood aggregation was assessed in 6 healthy male volunteers on 2 occasions (Day 1, Day 7) using the Chronolog aggregometer. From Day 2 up to Day 7, subjects received a daily oral dose of 75 mg ASA. The relationship between collagen dose and platelet aggregation response was assessed. On Day 1, maximal aggregation was observed at 1 μg/mL collagen (15.3 ± 4.6 Ω) and higher. Reproducible results were obtained without any indication of intra-subject fluctuations. ASA treatment decreased maximal aggregation by 80% and 38% at 0.5 and 2.0 μg/mL collagen, respectively. Power calculations were performed based on the observed intra-subject variability and demonstrated minimal sample sizes of 9 - 11 subjects for future cross-over ASA-drug interaction studies exploring effects on platelet aggregation, which demonstrates that the proposed collagen-induced ex vivo whole blood platelet aggregation is a feasible methodology to evaluate ASA-drug interactions in healthy volunteers.
Keywords	Platelet Aggregation ; Impedance Aggregometry ; Whole Blood ; Collagen ; Aspirin Interaction ; Medicine (General) ; R5-920 ; Medicine ; R
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Scientific Research Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Immunomonitoring of Tacrolimus in Healthy Volunteers

Aliede E. in ‘t Veld / Hendrika W. Grievink / Mahdi Saghari / Frederik E. Stuurman / Marieke L. de Kam / Aiko P. J. de Vries / Brenda C. M. de Winter / Jacobus Burggraaf / Adam F. Cohen / Matthijs Moerland

International Journal of Molecular Sciences, Vol 20, Iss 19, p

The First Step from PK- to PD-Based Therapeutic Drug Monitoring?

2019 Volume 4710

Abstract: Therapeutic drug monitoring is routinely performed to maintain optimal tacrolimus concentrations in kidney transplant recipients. Nonetheless, toxicity and rejection still occur within an acceptable concentration-range. To have a better understanding of ... ...

Abstract	Therapeutic drug monitoring is routinely performed to maintain optimal tacrolimus concentrations in kidney transplant recipients. Nonetheless, toxicity and rejection still occur within an acceptable concentration-range. To have a better understanding of the relationship between tacrolimus dose, tacrolimus concentration, and its effect on the target cell, we developed functional immune tests for the quantification of the tacrolimus effect. Twelve healthy volunteers received a single dose of tacrolimus, after which intracellular and whole blood tacrolimus concentrations were measured and were related to T cell functionality. A significant correlation was found between tacrolimus concentrations in T cells and whole blood concentrations (r = 0.71, p = 0.009), while no correlation was found between tacrolimus concentrations in peripheral blood mononuclear cells (PBMCs) and whole blood (r = 0.35, p = 0.27). Phytohemagglutinin (PHA) induced the production of IL-2 and IFNγ, as well as the inhibition of CD71 and CD154 expression on T cells at 1.5 h post-dose, when maximum tacrolimus levels were observed. Moreover, the in vitro tacrolimus effect of the mentioned markers corresponded with the ex vivo effect after dosing. In conclusion, our results showed that intracellular tacrolimus concentrations mimic whole blood concentrations, and that PHA-induced cytokine production (IL-2 and IFNγ) and activation marker expression (CD71 and CD154) are suitable readout measures to measure the immunosuppressive effect of tacrolimus on the T cell.
Keywords	immunosuppressive drugs ; transplantation ; pharmacodynamics ; pharmacokinetics ; tacrolimus ; therapeutic drug monitoring ; immunomonitoring ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Elevated expression of phospholipid transfer protein in bone marrow derived cells causes atherosclerosis.

Rien van Haperen / Hannelore Samyn / Matthijs Moerland / Teus van Gent / Marian Peeters / Frank Grosveld / Arie van Tol / Rini de Crom

PLoS ONE, Vol 3, Iss 5, p e

2008 Volume 2255

Abstract: BACKGROUND: Phospholipid transfer protein (PLTP) is expressed by various cell types. In plasma, it is associated with high density lipoproteins (HDL). Elevated levels of PLTP in transgenic mice result in decreased HDL and increased atherosclerosis. PLTP ... ...

Abstract	BACKGROUND: Phospholipid transfer protein (PLTP) is expressed by various cell types. In plasma, it is associated with high density lipoproteins (HDL). Elevated levels of PLTP in transgenic mice result in decreased HDL and increased atherosclerosis. PLTP is present in human atherosclerotic lesions, where it seems to be macrophage derived. The aim of the present study is to evaluate the atherogenic potential of macrophage derived PLTP. METHODS AND FINDINGS: Here we show that macrophages from human PLTP transgenic mice secrete active PLTP. Subsequently, we performed bone marrow transplantations using either wild type mice (PLTPwt/wt), hemizygous PLTP transgenic mice (huPLTPtg/wt) or homozygous PLTP transgenic mice (huPLTPtg/tg) as donors and low density lipoprotein receptor deficient mice (LDLR-/-) as acceptors, in order to establish the role of PLTP expressed by bone marrow derived cells in diet-induced atherogenesis. Atherosclerosis was increased in the huPLTPtg/wt-->LDLR-/- mice (2.3-fold) and even further in the huPLTPtg/tg-->LDLR-/- mice (4.5-fold) compared with the control PLTPwt/wt-->LDLR-/- mice (both P<0.001). Plasma PLTP activity levels and non-HDL cholesterol were increased and HDL cholesterol decreased compared with controls (all P<0.01). PLTP was present in atherosclerotic plaques in the mice as demonstrated by immunohistochemistry and appears to co-localize with macrophages. Isolated macrophages from PLTP transgenic mice do not show differences in cholesterol efflux or in cytokine production. Lipopolysaccharide activation of macrophages results in increased production of PLTP. This effect was strongly amplified in PLTP transgenic macrophages. CONCLUSIONS: We conclude that PLTP expression by bone marrow derived cells results in atherogenic effects on plasma lipids, increased PLTP activity, high local PLTP protein levels in the atherosclerotic lesions and increased atherosclerotic lesion size.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2008-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED