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Article ; Online: Extracellular Vesicles and Thrombosis

Konstantinos Zifkos / Christophe Dubois / Katrin Schäfer

International Journal of Molecular Sciences, Vol 22, Iss 9317, p

Update on the Clinical and Experimental Evidence

2021 Volume 9317

Abstract: Extracellular vesicles (EVs) compose a heterogenous group of membrane-derived particles, including exosomes, microvesicles and apoptotic bodies, which are released into the extracellular environment in response to proinflammatory or proapoptotic stimuli. ...

Abstract	Extracellular vesicles (EVs) compose a heterogenous group of membrane-derived particles, including exosomes, microvesicles and apoptotic bodies, which are released into the extracellular environment in response to proinflammatory or proapoptotic stimuli. From earlier studies suggesting that EV shedding constitutes a cellular clearance mechanism, it has become evident that EV formation, secretion and uptake represent important mechanisms of intercellular communication and exchange of a wide variety of molecules, with relevance in both physiological and pathological situations. The putative role of EVs in hemostasis and thrombosis is supported by clinical and experimental studies unraveling how these cell-derived structures affect clot formation (and resolution). From those studies, it has become clear that the prothrombotic effects of EVs are not restricted to the exposure of tissue factor (TF) and phosphatidylserines (PS), but also involve multiplication of procoagulant surfaces, cross-linking of different cellular players at the site of injury and transfer of activation signals to other cell types. Here, we summarize the existing and novel clinical and experimental evidence on the role and function of EVs during arterial and venous thrombus formation and how they may be used as biomarkers as well as therapeutic vectors.
Keywords	arterial ; endothelial cells ; extracellular vesicles ; thrombosis ; venous ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Endothelial-dependent S-Sulfhydration of tissue factor pathway inhibitor regulates blood coagulation

Janina Wittig / Maria-Kyriaki Drekolia / Anastasia Kyselova / Fredy Delgado Lagos / Magdalena L. Bochenek / Jiong Hu / Katrin Schäfer / Ingrid Fleming / Sofia-Iris Bibli

Redox Biology, Vol 62, Iss , Pp 102694- (2023)

2023

Abstract: Tissue factor pathway inhibitor (TFPI) is an important regulator of coagulation and a link between inflammation and thrombosis. Here we investigated whether endothelial cell-driven oxidative post-translational modifications could have an impact on TFPI ... ...

Abstract	Tissue factor pathway inhibitor (TFPI) is an important regulator of coagulation and a link between inflammation and thrombosis. Here we investigated whether endothelial cell-driven oxidative post-translational modifications could have an impact on TFPI activity. We focused on S-sulfhydration, which is a hydrogen sulfide-dependent post-translational modification that, in endothelial cells, is regulated by the enzyme cystathionine γ-lyase (CSE). The study made use of human primary endothelial cells and blood from healthy individuals or subjects with atherosclerosis as well as from mice lacking endothelial CSE. TFPI was S-sulfhydrated in endothelial cells from healthy individuals and mice, while the loss of endothelial CSE expression/activity reduced its modification. Non-S-sulfhydrated TFPI was no longer able to interact with factor Xa, which facilitated the activation of tissue factor. Similarly, non-S-sulfhydratable TFPI mutants bound less protein S, while supplementation with hydrogen sulfide donors, preserved TFPI activity. Phenotypically, loss of TFPI S-sulfhydration increased clot retraction, suggesting that this post-translational modification is a new endothelial cell-dependent mechanism that contributes to the regulation of blood coagulation.
Keywords	TFPI ; Endothelial CSE ; S-sulfhydration ; Coagulation ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: BMI and WHR Are Reflected in Female Facial Shape and Texture

Christine Mayer / Sonja Windhager / Katrin Schaefer / Philipp Mitteroecker

PLoS ONE, Vol 12, Iss 1, p e

A Geometric Morphometric Image Analysis.

2017 Volume 0169336

Abstract: Facial markers of body composition are frequently studied in evolutionary psychology and are important in computational and forensic face recognition. We assessed the association of body mass index (BMI) and waist-to-hip ratio (WHR) with facial shape and ...

Abstract	Facial markers of body composition are frequently studied in evolutionary psychology and are important in computational and forensic face recognition. We assessed the association of body mass index (BMI) and waist-to-hip ratio (WHR) with facial shape and texture (color pattern) in a sample of young Middle European women by a combination of geometric morphometrics and image analysis. Faces of women with high BMI had a wider and rounder facial outline relative to the size of the eyes and lips, and relatively lower eyebrows. Furthermore, women with high BMI had a brighter and more reddish skin color than women with lower BMI. The same facial features were associated with WHR, even though BMI and WHR were only moderately correlated. Yet BMI was better predictable than WHR from facial attributes. After leave-one-out cross-validation, we were able to predict 25% of variation in BMI and 10% of variation in WHR by facial shape. Facial texture predicted only about 3-10% of variation in BMI and WHR. This indicates that facial shape primarily reflects total fat proportion, rather than the distribution of fat within the body. The association of reddish facial texture in high-BMI women may be mediated by increased blood pressure and superficial blood flow as well as diet. Our study elucidates how geometric morphometric image analysis serves to quantify the effect of biological factors such as BMI and WHR to facial shape and color, which in turn contributes to social perception.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Deletion of endothelial leptin receptors in mice promotes diet-induced obesity

Rajinikanth Gogiraju / Claudius Witzler / Fatemeh Shahneh / Astrid Hubert / Luisa Renner / Magdalena L. Bochenek / Konstantinos Zifkos / Christian Becker / Madhusudhan Thati / Katrin Schäfer

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 17

Abstract: Abstract Obesity promotes endothelial dysfunction. Endothelial cells not only respond, but possibly actively promote the development of obesity and metabolic dysfunction. Our aim was to characterize the role of endothelial leptin receptors (LepR) for ... ...

Abstract	Abstract Obesity promotes endothelial dysfunction. Endothelial cells not only respond, but possibly actively promote the development of obesity and metabolic dysfunction. Our aim was to characterize the role of endothelial leptin receptors (LepR) for endothelial and whole body metabolism and diet-induced obesity. Mice with tamoxifen-inducible, Tie2.Cre-ERT2-mediated deletion of LepR in endothelial cells (End.LepR knockout, KO) were fed high-fat diet (HFD) for 16 weeks. Body weight gain, serum leptin levels, visceral adiposity and adipose tissue inflammation were more pronounced in obese End.LepR-KO mice, whereas fasting serum glucose and insulin levels or the extent of hepatic steatosis did not differ. Reduced brain endothelial transcytosis of exogenous leptin, increased food intake and total energy balance were observed in End.LepR-KO mice and accompanied by brain perivascular macrophage accumulation, whereas physical activity, energy expenditure and respiratory exchange rates did not differ. Metabolic flux analysis revealed no changes in the bioenergetic profile of endothelial cells from brain or visceral adipose tissue, but higher glycolysis and mitochondrial respiration rates in those isolated from lungs. Our findings support a role for endothelial LepRs in the transport of leptin into the brain and neuronal control of food intake, and also suggest organ-specific changes in endothelial cell, but not whole-body metabolism.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function

Janina Krug / Magdalena L. Bochenek / Rajinikanth Gogiraju / Dagmar Laubert-Reh / Karl J. Lackner / Thomas Münzel / Philipp S. Wild / Christine Espinola-Klein / Katrin Schäfer

Biomedicines, Vol 11, Iss 2459, p

2023 Volume 2459

Abstract: 1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is ... ...

Abstract	(1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is unknown. We have recently shown in mice that reduced endothelial protein C receptor (EPCR) expression results in defective angiogenesis following experimental hindlimb ischemia. (2) Purpose: To determine soluble (s)EPCR levels in the plasma of patients with PAD and to compare them with the protein C activity and biomarkers of endothelial function, inflammation, and angiogenesis. (3) Methods and Results: Clinical tests of vascular function and immunoassays of plasma from patients with PAD stage II were compared to age- and sex-matched individuals with and without cardiovascular risk factors or PAD stage III/IV patients. sEPCR levels were significantly lower in PAD stage II patients compared to subjects with risk factors, but no PAD, and further decreased in PAD stage III/IV patients. Plasma protein C activity or levels of ADAM17, a mediator of EPCR shedding, did not differ. Significant associations between sEPCR and the ankle-brachial index ( p = 0.0359), age ( p = 0.0488), body mass index ( p = 0.0110), and plasma sE-selectin levels ( p = 0.0327) were observed. High-sensitive CRP levels and white blood cell counts were significantly elevated in PAD patients and associated with serum glucose levels, but not sEPCR. In contrast, plasma TNFα or IL1β levels did not differ. Circulating levels of VEGF were significantly elevated in PAD stage II patients ( p = 0.0198), but not associated with molecular (sE-selectin) or functional (ankle-brachial index) markers of vascular health. (4) Conclusions: Our findings suggest that circulating sEPCR levels may be useful as biomarkers of endothelial dysfunction, including angiogenesis, in persons older than 35 years and that progressive loss of endothelial protein C receptors might be involved in the development and progression of PAD.
Keywords	angiogenesis ; coagulation ; endothelium ; ischemia ; peripheral artery disease ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Calibrating facial morphs for use as stimuli in biological studies of social perception

Sonja Windhager / Fred L. Bookstein / Hanna Mueller / Elke Zunner / Sylvia Kirchengast / Katrin Schaefer

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 9

Abstract: Abstract Studies of human social perception become more persuasive when the behavior of raters can be separated from the variability of the stimuli they are rating. We prototype such a rigorous analysis for a set of five social ratings of faces varying ... ...

Abstract	Abstract Studies of human social perception become more persuasive when the behavior of raters can be separated from the variability of the stimuli they are rating. We prototype such a rigorous analysis for a set of five social ratings of faces varying by body fat percentage (BFP). 274 raters of both sexes in three age groups (adolescent, young adult, senior) rated five morphs of the same averaged facial image warped to the positions of 72 landmarks and semilandmarks predicted by linear regression on BFP at five different levels (the average, ±2 SD, ±5 SD). Each subject rated all five morphs for maturity, dominance, masculinity, attractiveness, and health. The patterns of dependence of ratings on the BFP calibration differ for the different ratings, but not substantially across the six groups of raters. This has implications for theories of social perception, specifically, the relevance of individual rater scale anchoring. The method is also highly relevant for other studies on how biological facial variation affects ratings.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Associations of physical strength with facial shape in an African pastoralist society, the Maasai of Northern Tanzania.

Marina L Butovskaya / Sonja Windhager / Dimitri Karelin / Anna Mezentseva / Katrin Schaefer / Bernhard Fink

PLoS ONE, Vol 13, Iss 5, p e

2018 Volume 0197738

Abstract: OBJECTIVES:Previous research has documented associations of physical strength and facial morphology predominantly in men of Western societies. Faces of strong men tend to be more robust, are rounder and have a prominent jawline compared with faces of ... ...

Abstract	OBJECTIVES:Previous research has documented associations of physical strength and facial morphology predominantly in men of Western societies. Faces of strong men tend to be more robust, are rounder and have a prominent jawline compared with faces of weak men. Here, we investigate whether the morphometric patterns of strength-face relationships reported for members of industrialized societies can also be found in members of an African pastoralist society, the Maasai of Northern Tanzania. MATERIALS AND METHODS:Handgrip strength (HGS) measures and facial photographs were collected from a sample of 185 men and 120 women of the Maasai in the Ngorongoro Conservation Area. In young-adults (20-29 years; n = 95) and mid-adults (30-50 years; n = 114), we digitized 71 somatometric landmarks and semilandmarks to capture variation in facial morphology and performed shape regressions of landmark coordinates upon HGS. Results were visualized in the form of thin-plate plate spline deformation grids and geometric morphometric morphs. RESULTS:Individuals with higher HGS tended to have wider faces with a lower and broader forehead, a wider distance between the medial canthi of the eyes, a wider nose, fuller lips, and a larger, squarer lower facial outline compared with weaker individuals of the same age-sex group. In mid-adult men, these associations were weaker than in the other age-sex groups. DISCUSSION:We conclude that the patterns of HGS relationships with face shape in the Maasai are similar to those reported from related investigations in samples of industrialized societies. We discuss differences between the present and related studies with regard to knowledge about the causes for age- and sex-related facial shape variation and physical strength associations.
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: EPCR-PAR1 biased signaling regulates perfusion recovery and neovascularization in peripheral ischemia

Magdalena L. Bochenek / Rajinikanth Gogiraju / Stefanie Großmann / Janina Krug / Jennifer Orth / Sabine Reyda / George S. Georgiadis / Henri M. Spronk / Stavros Konstantinides / Thomas Münzel / John H. Griffin / Philipp Wild / Christine Espinola-Klein / Wolfram Ruf / Katrin Schäfer

JCI Insight, Vol 7, Iss

2022 Volume 14

Abstract: Blood clot formation initiates ischemic events, but coagulation roles during postischemic tissue repair are poorly understood. The endothelial protein C receptor (EPCR) regulates coagulation, as well as immune and vascular signaling, by protease ... ...

Abstract	Blood clot formation initiates ischemic events, but coagulation roles during postischemic tissue repair are poorly understood. The endothelial protein C receptor (EPCR) regulates coagulation, as well as immune and vascular signaling, by protease activated receptors (PARs). Here, we show that endothelial EPCR-PAR1 signaling supports reperfusion and neovascularization in hindlimb ischemia in mice. Whereas deletion of PAR2 or PAR4 did not impair angiogenesis, EPCR and PAR1 deficiency or PAR1 resistance to cleavage by activated protein C caused markedly reduced postischemic reperfusion in vivo and angiogenesis in vitro. These findings were corroborated by biased PAR1 agonism in isolated primary endothelial cells. Loss of EPCR-PAR1 signaling upregulated hemoglobin expression and reduced endothelial nitric oxide (NO) bioavailability. Defective angiogenic sprouting was rescued by the NO donor DETA-NO, whereas NO scavenging increased hemoglobin and mesenchymal marker expression in human and mouse endothelial cells. Vascular specimens from patients with ischemic peripheral artery disease exhibited increased hemoglobin expression, and soluble EPCR and NO levels were reduced in plasma. Our data implicate endothelial EPCR-PAR1 signaling in the hypoxic response of endothelial cells and identify suppression of hemoglobin expression as an unexpected link between coagulation signaling, preservation of endothelial cell NO bioavailability, support of neovascularization, and prevention of fibrosis.
Keywords	Angiogenesis ; Vascular biology ; Medicine ; R
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The morphometrics of "masculinity" in human faces.

Philipp Mitteroecker / Sonja Windhager / Gerd B Müller / Katrin Schaefer

PLoS ONE, Vol 10, Iss 2, p e

2015 Volume 0118374

Abstract: In studies of social inference and human mate preference, a wide but inconsistent array of tools for computing facial masculinity has been devised. Several of these approaches implicitly assumed that the individual expression of sexually dimorphic shape ... ...

Abstract	In studies of social inference and human mate preference, a wide but inconsistent array of tools for computing facial masculinity has been devised. Several of these approaches implicitly assumed that the individual expression of sexually dimorphic shape features, which we refer to as maleness, resembles facial shape features perceived as masculine. We outline a morphometric strategy for estimating separately the face shape patterns that underlie perceived masculinity and maleness, and for computing individual scores for these shape patterns. We further show how faces with different degrees of masculinity or maleness can be constructed in a geometric morphometric framework. In an application of these methods to a set of human facial photographs, we found that shape features typically perceived as masculine are wide faces with a wide inter-orbital distance, a wide nose, thin lips, and a large and massive lower face. The individual expressions of this combination of shape features--the masculinity shape scores--were the best predictor of rated masculinity among the compared methods (r = 0.5). The shape features perceived as masculine only partly resembled the average face shape difference between males and females (sexual dimorphism). Discriminant functions and Procrustes distances to the female mean shape were poor predictors of perceived masculinity.
Keywords	Medicine ; R ; Science ; Q
Subject code	400
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The gut microbiota instructs the hepatic endothelial cell transcriptome

Henning Formes / Joana P. Bernardes / Amrit Mann / Franziska Bayer / Giulia Pontarollo / Klytaimnistra Kiouptsi / Katrin Schäfer / Sebastian Attig / Teodora Nikolova / Thomas G. Hofmann / Jörn M. Schattenberg / Hristo Todorov / Susanne Gerber / Philip Rosenstiel / Tobias Bopp / Felix Sommer / Christoph Reinhardt

iScience, Vol 24, Iss 10, Pp 103092- (2021)

2021

Abstract: Summary: The gut microbiota affects remote organ functions but its impact on organotypic endothelial cell (EC) transcriptomes remains unexplored. The liver endothelium encounters microbiota-derived signals and metabolites via the portal circulation. To ... ...

Abstract	Summary: The gut microbiota affects remote organ functions but its impact on organotypic endothelial cell (EC) transcriptomes remains unexplored. The liver endothelium encounters microbiota-derived signals and metabolites via the portal circulation. To pinpoint how gut commensals affect the hepatic sinusoidal endothelium, a magnetic cell sorting protocol, combined with fluorescence-activated cell sorting, was used to isolate hepatic sinusoidal ECs from germ-free (GF) and conventionally raised (CONV-R) mice for transcriptome analysis by RNA sequencing. This resulted in a comprehensive map of microbiota-regulated hepatic EC-specific transcriptome profiles. Gene Ontology analysis revealed that several functional processes in the hepatic endothelium were affected. The absence of microbiota influenced the expression of genes involved in cholesterol flux and angiogenesis. Specifically, genes functioning in hepatic endothelial sphingosine metabolism and the sphingosine-1-phosphate pathway showed drastically increased expression in the GF state. Our analyses reveal a prominent role for the microbiota in shaping the transcriptional landscape of the hepatic endothelium.
Keywords	Hepatology ; Microbiome ; Transcriptomics ; Science ; Q
Subject code	570
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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