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  1. Article ; Online: Pancreatic Islets as a Target of Adipokines.

    Reiterer, Moritz / Gilani, Ankit / Lo, James C

    Comprehensive Physiology

    2022  Volume 12, Issue 3, Page(s) 4039–4065

    Abstract: Rising rates of obesity are intricately tied to the type 2 diabetes epidemic. The adipose tissues can play a central role in protection against or triggering metabolic diseases through the secretion of adipokines. Many adipokines may improve peripheral ... ...

    Abstract Rising rates of obesity are intricately tied to the type 2 diabetes epidemic. The adipose tissues can play a central role in protection against or triggering metabolic diseases through the secretion of adipokines. Many adipokines may improve peripheral insulin sensitivity through a variety of mechanisms, thereby indirectly reducing the strain on beta cells and thus improving their viability and functionality. Such effects will not be the focus of this article. Rather, we will focus on adipocyte-secreted molecules that have a direct effect on pancreatic islets. By their nature, adipokines represent potential druggable targets that can reach the islets and improve beta-cell function or preserve beta cells in the face of metabolic stress. © 2022 American Physiological Society. Compr Physiol 12:1-27, 2022.
    MeSH term(s) Adipocytes ; Adipokines/metabolism ; Adipose Tissue/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Humans ; Insulin-Secreting Cells/metabolism
    Chemical Substances Adipokines
    Language English
    Publishing date 2022-08-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2040-4603
    ISSN (online) 2040-4603
    DOI 10.1002/cphy.c210044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Protocol to isolate and culture primary mouse feto-placental endothelial cells.

    Sandovici, Ionel / Reiterer, Moritz / Constância, Miguel / Branco, Cristina M

    STAR protocols

    2022  Volume 3, Issue 4, Page(s) 101721

    Abstract: In the mouse, feto-placental endothelial cells (FPEC) line the inner surface of the feto-placental blood vessels located within placental labyrinthine zone and play critical roles in placental development and function. Here, we present a detailed ... ...

    Abstract In the mouse, feto-placental endothelial cells (FPEC) line the inner surface of the feto-placental blood vessels located within placental labyrinthine zone and play critical roles in placental development and function. Here, we present a detailed protocol for isolation and culture of primary mouse FPEC, as well as two complementary methods (immunohistochemistry staining and flow cytometry analysis) to assess their purity. These cells are suitable for downstream ex vivo studies to investigate their functional properties, both in normal and pathological contexts. For complete details on the use and execution of this protocol, please refer to Sandovici et al. (2022).
    MeSH term(s) Female ; Pregnancy ; Animals ; Mice ; Endothelial Cells ; Placenta ; Flow Cytometry
    Language English
    Publishing date 2022-09-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101721
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Endothelial cells and organ function: applications and implications of understanding unique and reciprocal remodelling

    Reiterer, Moritz / Branco, Cristina M

    FEBS journal. 2020 Mar., v. 287, no. 6

    2020  

    Abstract: The microvasculature is a heterogeneous, dynamic and versatile component of the systemic circulation, with a unique ability to locally self‐regulate and to respond to organ demand and environmental stimuli. Endothelial cells from different organs display ...

    Abstract The microvasculature is a heterogeneous, dynamic and versatile component of the systemic circulation, with a unique ability to locally self‐regulate and to respond to organ demand and environmental stimuli. Endothelial cells from different organs display considerable variation, but it is currently unclear to what extent functional properties of organ‐specific endothelial cells are intrinsic, acquired and/or reprogrammable. Vascular function is a fundamental pillar of homeostasis, and dysfunction results in systemic consequences for the organism. Additionally, vascular failure can occur downstream of organ disease or environmental stress, often driving an exacerbation of symptoms and pathologies originally independent of the local circulation. The understanding of the molecular mechanisms underlying endothelial physiology and metabolism holds the promise to inform and improve diagnosis, prognosis and treatment options for a myriad of conditions as unrelated as cancer, neurodegeneration or pulmonary hypertension, and likely everything in between, if we consider that also treatments for such conditions are primarily distributed via the bloodstream. However, studying endothelial function has its challenges: the origin, isolation, culture conditions and preconditioning stimuli make this an extremely variable cell type to study and difficult to source. Animal models exist but are neither trivial to generate, nor necessarily adequately translatable to human disease. In this article, we aim to illustrate the breadth of microvascular functions in different environments, highlighting current and pioneering studies that have advanced our insight into the importance of the integrity of this tissue, as well as the limitations posed by its heterogeneity and plasticity.
    Keywords animals ; blood flow ; homeostasis ; human diseases ; hypertension ; metabolism ; neurodegenerative diseases ; plasticity ; prognosis
    Language English
    Dates of publication 2020-03
    Size p. 1088-1100.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note NAL-AP-2-clean ; JOURNAL ARTICLE
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.15143
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Hyperoxia Reprogrammes Microvascular Endothelial Cell Response to Hypoxia in an Organ-Specific Manner.

    Reiterer, Moritz / Eakin, Amanda / Johnson, Randall S / Branco, Cristina M

    Cells

    2022  Volume 11, Issue 16

    Abstract: Organ function relies on microvascular networks to maintain homeostatic equilibrium, which varies widely in different organs and during different physiological challenges. The endothelium role in this critical process can only be evaluated in ... ...

    Abstract Organ function relies on microvascular networks to maintain homeostatic equilibrium, which varies widely in different organs and during different physiological challenges. The endothelium role in this critical process can only be evaluated in physiologically relevant contexts. Comparing the responses to oxygen flux in primary murine microvascular EC (MVEC) obtained from brain and lung tissue reveals that supra-physiological oxygen tensions can compromise MVEC viability. Brain MVEC lose mitochondrial activity and undergo significant alterations in electron transport chain (ETC) composition when cultured under standard, non-physiological atmospheric oxygen levels. While glycolytic capacity of both lung and brain MVEC are unchanged by environmental oxygen, the ability to trigger a metabolic shift when oxygen levels drop is greatly compromised following exposure to hyperoxia. This is particularly striking in MVEC from the brain. This work demonstrates that the unique metabolism and function of organ-specific MVEC (1) can be reprogrammed by external oxygen, (2) that this reprogramming can compromise MVEC survival and, importantly, (3) that ex vivo modelling of endothelial function is significantly affected by culture conditions. It further demonstrates that physiological, metabolic and functional studies performed in non-physiological environments do not represent cell function in situ, and this has serious implications in the interpretation of cell-based pre-clinical models.
    MeSH term(s) Animals ; Endothelial Cells/metabolism ; Hyperoxia ; Hypoxia/metabolism ; Mice ; Microvessels ; Oxygen/metabolism
    Chemical Substances Oxygen (S88TT14065)
    Language English
    Publishing date 2022-08-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11162469
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Endothelial cells and organ function: applications and implications of understanding unique and reciprocal remodelling.

    Reiterer, Moritz / Branco, Cristina M

    The FEBS journal

    2019  Volume 287, Issue 6, Page(s) 1088–1100

    Abstract: The microvasculature is a heterogeneous, dynamic and versatile component of the systemic circulation, with a unique ability to locally self-regulate and to respond to organ demand and environmental stimuli. Endothelial cells from different organs display ...

    Abstract The microvasculature is a heterogeneous, dynamic and versatile component of the systemic circulation, with a unique ability to locally self-regulate and to respond to organ demand and environmental stimuli. Endothelial cells from different organs display considerable variation, but it is currently unclear to what extent functional properties of organ-specific endothelial cells are intrinsic, acquired and/or reprogrammable. Vascular function is a fundamental pillar of homeostasis, and dysfunction results in systemic consequences for the organism. Additionally, vascular failure can occur downstream of organ disease or environmental stress, often driving an exacerbation of symptoms and pathologies originally independent of the local circulation. The understanding of the molecular mechanisms underlying endothelial physiology and metabolism holds the promise to inform and improve diagnosis, prognosis and treatment options for a myriad of conditions as unrelated as cancer, neurodegeneration or pulmonary hypertension, and likely everything in between, if we consider that also treatments for such conditions are primarily distributed via the bloodstream. However, studying endothelial function has its challenges: the origin, isolation, culture conditions and preconditioning stimuli make this an extremely variable cell type to study and difficult to source. Animal models exist but are neither trivial to generate, nor necessarily adequately translatable to human disease. In this article, we aim to illustrate the breadth of microvascular functions in different environments, highlighting current and pioneering studies that have advanced our insight into the importance of the integrity of this tissue, as well as the limitations posed by its heterogeneity and plasticity.
    MeSH term(s) Animals ; Endothelial Cells/metabolism ; Endothelium, Vascular/cytology ; Endothelium, Vascular/physiology ; Humans
    Language English
    Publishing date 2019-12-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.15143
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Object Semantic Segmentation in Point Clouds—Comparison of a Deep Learning and a Knowledge-Based Method

    Jean-Jacques Ponciano / Moritz Roetner / Alexander Reiterer / Frank Boochs

    ISPRS International Journal of Geo-Information, Vol 10, Iss 256, p

    2021  Volume 256

    Abstract: Through the power of new sensing technologies, we are increasingly digitizing the real world. However, instruments produce unstructured data, mainly in the form of point clouds for 3D data and images for 2D data. Nevertheless, many applications (such as ... ...

    Abstract Through the power of new sensing technologies, we are increasingly digitizing the real world. However, instruments produce unstructured data, mainly in the form of point clouds for 3D data and images for 2D data. Nevertheless, many applications (such as navigation, survey, infrastructure analysis) need structured data containing objects and their geometry. Various computer vision approaches have thus been developed to structure the data and identify objects therein. They can be separated into model-driven, data-driven, and knowledge-based approaches. Model-driven approaches mainly use the information on the objects contained in the data and are thus limited to objects and context. Among data-driven approaches, we increasingly find deep learning strategies because of their autonomy in detecting objects. They identify reliable patterns in the data and connect these to the object of interest. Deep learning approaches have to learn these patterns in a training stage. Knowledge-based approaches use characteristic knowledge from different domains allowing the detection and classification of objects. The knowledge must be formalized and substitutes the training for deep learning. Semantic web technologies allow the management of such human knowledge. Deep learning and knowledge-based approaches have already shown good results for semantic segmentation in various examples. The common goal but the different strategies of the two approaches engaged our interest in doing a comparison to get an idea of their strengths and weaknesses. To fill this knowledge gap, we applied two implementations of such approaches to a mobile mapping point cloud. The detected object categories are car, bush, tree, ground, streetlight and building. The deep learning approach uses a convolutional neural network, whereas the knowledge-based approach uses standard semantic web technologies such as SPARQL and OWL2to guide the data processing and the subsequent classification as well. The LiDAR point cloud used was acquired by a mobile mapping system ...
    Keywords point cloud ; deep learning ; knowledge-based ; SPARQL ; segmentation ; 3D ; Geography (General) ; G1-922
    Subject code 004
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Author Correction: Acute and chronic hypoxia differentially predispose lungs for metastases.

    Reiterer, Moritz / Colaço, Renato / Emrouznejad, Pardis / Jensen, Anders / Rundqvist, Helene / Johnson, Randall S / Branco, Cristina

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 1627

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Language English
    Publishing date 2020-01-28
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-58616-0
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  8. Article ; Online: Author Correction

    Moritz Reiterer / Renato Colaço / Pardis Emrouznejad / Anders Jensen / Helene Rundqvist / Randall S. Johnson / Cristina Branco

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    Acute and chronic hypoxia differentially predispose lungs for metastases

    2020  Volume 6

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: MICROVASCULAR ENDOTHELIAL CELL ADAPTATION TO HYPOXIA IS ORGAN-SPECIFIC AND CONDITIONED BY ENVIRONMENTAL OXYGEN

    Reiterer, Moritz / Eakin, Amanda J / Burke, Aileen / Johnson, Randall S / Branco, Cristina M

    bioRxiv

    Abstract: Microvascular endothelial cells (MVEC) are plastic, versatile and highly responsive cells, with morphological and functional aspects that uniquely match the tissues they supply. The response of these cells to oxygen oscillations is an essential aspect of ...

    Abstract Microvascular endothelial cells (MVEC) are plastic, versatile and highly responsive cells, with morphological and functional aspects that uniquely match the tissues they supply. The response of these cells to oxygen oscillations is an essential aspect of tissue homeostasis, and is finely tuned to maintain organ function during physiological and metabolic challenges. Primary MVEC from two continuous capillary networks with distinct organ microenvironments, those of the lung and brain, were pre-conditioned at normal atmospheric (∼ 21 %) and physiological (5 and 10 %) O2 levels, and subsequently used to compare organ-specific MVEC hypoxia response. Brain MVEC preferentially stabilise HIF-2α in response to hypoxia, whereas lung MVEC primarily accumulate HIF-1α; however, this does not result in significant differences at the level of transcriptional activation of hypoxia-induced genes. Glycolytic activity is comparable between brain and lung endothelial cells, and is affected by oxygen pre-conditioning, while glucose uptake is not changed by oxygen pre-conditioning and is observed to be consistently higher in brain MVEC. Conversely, MVEC mitochondrial activity is organ-specific; brain MVEC maintain a higher relative mitochondrial spare capacity at 5% O2, but not following hyperoxic priming. If maintained at supra-physiological O2 levels, both MVEC fail to respond to hypoxia, and have severely compromised and delayed induction of the glycolytic shifts required for survival, an effect which is particularly pronounced in brain MVEC. Oxygen preconditioning also differentially shapes the composition of the mitochondrial electron transport chain (ETC) in the two MVEC populations. Lung MVEC primed at physioxia have lower levels of all ETC complexes compared to hyperoxia, an effect exacerbated by hypoxia. Conversely, brain MVEC expanded in physioxia display increased complex II (SDH) activity, which is further augmented during hypoxia. SDH activity in brain MVEC primed at 21 % O2 is ablated; upon hypoxia, this results in the accumulation of near-toxic levels of succinate in these cells. Our data suggests that, even though MVEC are primarily glycolytic, mitochondrial integrity in brain MVEC is essential for metabolic responses to hypoxia; these responses are compromised when cells are exposed to supra-physiological levels of oxygen. This work demonstrates that the study of MVEC in normal cell culture environments do not adequately represent physiological parameters found in situ, and show that the unique metabolism and function of organ-specific MVEC can be reprogrammed by external oxygen, significantly affecting the timing and degree of downstream responses. Graphical Abstract In brief Hypoxia sensing by microvascular endothelial cells (MVEC) is organ-specific, and efficacy of response is affected by external oxygen. While glycolytic capacity is mostly maintained in MVEC regardless of organ or origin, mitochondrial function is required for adequate sensing and timely metabolic shift to glycolysis. Hyperoxygenation of MVEC compromises mitochondrial function, glycolytic shift and survival to hypoxia. Highlights Environmental O2 influences MVEC hypoxia response in an organ-specific fashion Brain MVEC are unable to respond and survive to hypoxia if hyperoxygenated prior to stress MVEC glycolytic capacity is not affected by O2, but the increase in glucose uptake and shift to glycolytic metabolism stifled and delayed in hyperoxidized MVEC High O2 ablates activity of mitochondria complex II in brain MVEC, significantly disturbing succinate levels Disruption of mitochondrial integrity compromises hypoxia sensing irrespective of glycolytic capacity
    Keywords covid19
    Publisher BioRxiv
    Document type Article ; Online
    DOI 10.1101/2020.08.25.265926
    Database COVID19

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  10. Article ; Online: Acute and chronic hypoxia differentially predispose lungs for metastases.

    Reiterer, Moritz / Colaço, Renato / Emrouznejad, Pardis / Jensen, Anders / Rundqvist, Helene / Johnson, Randall S / Branco, Cristina

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 10246

    Abstract: Oscillations in oxygen levels affect malignant cell growth, survival, and metastasis, but also somatic cell behaviour. In this work, we studied the effect of the differential expression of the two primary hypoxia inducible transcription factor isoforms, ... ...

    Abstract Oscillations in oxygen levels affect malignant cell growth, survival, and metastasis, but also somatic cell behaviour. In this work, we studied the effect of the differential expression of the two primary hypoxia inducible transcription factor isoforms, HIF-1α and HIF-2α, and pulmonary hypoxia to investigate how the hypoxia response of the vascular endothelium remodels the lung pre-metastatic niche. Molecular responses to acute versus chronic tissue hypoxia have been proposed to involve dynamic HIF stabilization, but the downstream consequences and the extent to which differential lengths of exposure to hypoxia can affect HIF-isoform activation and secondary organ pre-disposition for metastasis is unknown. We used primary pulmonary endothelial cells and mouse models with pulmonary endothelium-specific deletion of HIF-1α or HIF-2α, to characterise their roles in vascular integrity, inflammation and metastatic take after acute and chronic hypoxia. We found that acute hypoxic response results in increased lung metastatic tumours, caused by HIF-1α-dependent endothelial cell death and increased microvascular permeability, in turn facilitating extravasation. This is potentiated by the recruitment and retention of specific myeloid cells that further support a pro-metastatic environment. We also found that chronic hypoxia delays tumour growth to levels similar to those seen in normoxia, and in a HIF-2α-specific fashion, correlating with increased endothelial cell viability and vascular integrity. Deletion of endothelial HIF-2α rendered the lung environment more vulnerable to tumour cell seeding and growth. These results demonstrate that the nature of the hypoxic challenge strongly influences the nature of the endothelial cell response, and affects critical parameters of the pulmonary microenvironment, significantly impacting metastatic burden. Additionally, this work establishes endothelial cells as important players in lung remodelling and metastatic progression.
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Hypoxia/physiology ; Cell Survival ; Disease Susceptibility/metabolism ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Female ; Genotype ; Hypoxia/metabolism ; Hypoxia/physiopathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Lung/metabolism ; Lung/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Metastasis/physiopathology ; Oxygen/metabolism ; Primary Cell Culture ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Basic Helix-Loop-Helix Transcription Factors ; Hypoxia-Inducible Factor 1, alpha Subunit ; Vascular Endothelial Growth Factor A ; Oxygen (S88TT14065)
    Language English
    Publishing date 2019-07-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-46763-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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