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  1. Article ; Online: Poiseuille Gold Medal Awardee 2023.

    Lipowsky, Herbert H / Cooke, Brian M

    Biorheology

    2024  Volume 59, Issue 3-4, Page(s) 61–62

    MeSH term(s) Awards and Prizes
    Language English
    Publishing date 2024-03-08
    Publishing country Netherlands
    Document type Editorial
    ZDB-ID 82015-5
    ISSN 1878-5034 ; 0006-355X
    ISSN (online) 1878-5034
    ISSN 0006-355X
    DOI 10.3233/BIR-240006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Relative shedding of glycosaminoglycans from the endothelial glycocalyx during inflammation and their contribution to stiffness of the glycocalyx.

    Lipowsky, Herbert H

    Biorheology

    2019  Volume 56, Issue 2-3, Page(s) 191–205

    Abstract: Background: The endothelial (EC) surface layer (glycocalyx) has been shown to act as a barrier to transvascular exchange of solutes, and adhesion of leukocytes (WBCs) during the inflammatory process. It is a labile structure whose components are readily ...

    Abstract Background: The endothelial (EC) surface layer (glycocalyx) has been shown to act as a barrier to transvascular exchange of solutes, and adhesion of leukocytes (WBCs) during the inflammatory process. It is a labile structure whose components are readily shed by the action of proteases and endoglycosidases. Details of shedding of specific constituents of the glycocalyx remain to be determined.
    Objectives: To review the contributions of the primary glycosaminoglycans that comprise the glycocalyx, heparan sulfate (HS), chondroitin sulfate (CS) and hyaluronan (HA), as barrier to WBC-EC adhesion, and elucidate the rates of shedding of each component in response to an inflammatory stimulus. Assess the potential role that stiffness of the glycocalyx plays in resisting infiltration by WBCs during the adhesion process.
    Methods: Quantitate shedding of the glycocalyx in post-capillary venules of rat mesentery in response to superfusion of the tissue with 10-6 M fMLP. The presence and loss of HS, CS and HA was assessed by labeling all components with fluorescently labelled lectin (BS-1) or HS antibodies, and HA with fluorescently labelled hyaluronan binding protein (HBP).
    Results: Following a 30 min exposure of the mesentery to fMLP about 50% of HBP was lost in contrast to a previously shown loss of 20% of lectin labelled GAGs, and 25% loss of Mab labelled HS. The time constant for HBP shedding (5.8 min) was one-third that for BS-1 labelled GAGs (14.3 min). An attempt was made to assess stiffness of the glycocalyx by observing the motion of adhered lectin coated fluorescently labelled microspheres (FLM) under oscillatory flow conditions. Estimates of the elastic modulus of the glycocalyx revealed a value of 26 mPa, which was orders of magnitude below published data obtained by atomic force microscopy.
    Conclusions: The relatively rapid shedding of HA compared to HS was consistent with the hypothesis that HA may form the dominant barrier to WBC-EC adhesion. Prior observations that HA lies closer to and parallel to the endothelial membrane, compared to HS suggests that the compact layer of HA near the EC membrane surrounds WBC adhesion receptors that are much shorter in length than the total thickness of the glycocalyx. The relatively low elastic modulus of the glycocalyx under shear is consistent with the hypothesis that the FLMs adhered to strands of HS normal to the EC surface that extended above the relatively more compact and stiffer HA layer below. Gradients of stiffness within the glycocalyx may not be detected by compressive indentation tests published to date.
    MeSH term(s) Animals ; Cell Adhesion/physiology ; Elasticity ; Endothelial Cells/metabolism ; Erythrocytes/physiology ; Glycocalyx/metabolism ; Glycosaminoglycans/metabolism ; Inflammation/metabolism ; Leukocytes/physiology ; Male ; Microcirculation/physiology ; Periodicity ; Porosity ; Rats, Wistar ; Shear Strength
    Chemical Substances Glycosaminoglycans
    Language English
    Publishing date 2019-11-09
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 82015-5
    ISSN 1878-5034 ; 0006-355X
    ISSN (online) 1878-5034
    ISSN 0006-355X
    DOI 10.3233/BIR-190225
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Role of the Glycocalyx as a Barrier to Leukocyte-Endothelium Adhesion.

    Lipowsky, Herbert H

    Advances in experimental medicine and biology

    2018  Volume 1097, Page(s) 51–68

    Abstract: Leukocyte (WBC) to endothelial cell (EC) adhesion is a receptor-mediated process governed by the avidity and affinity of selectins, which modulate adhesive forces during WBC rolling, and integrins, which determine the strength of firm adhesion. Adhesion ... ...

    Abstract Leukocyte (WBC) to endothelial cell (EC) adhesion is a receptor-mediated process governed by the avidity and affinity of selectins, which modulate adhesive forces during WBC rolling, and integrins, which determine the strength of firm adhesion. Adhesion receptors on the EC surface lie below an endothelial surface layer (ESL) comprised of the EC glycocalyx and adsorbed proteins which, in vivo, have a thickness on the order 500 nm. The glycocalyx consists of a matrix of the glycosaminoglycans heparan sulfate and chondroitin sulfate, bound to proteoglycans and encased in hyaluronan. Together, these carbohydrates form a layer that varies in glycan content along the length of post-capillary venules where WBC-EC adhesion occurs. Thickness and porosity of the glycocalyx can vary dramatically during the inflammatory response as observed by increased infiltration and diffusion of macromolecules within the layer following activation of the EC by cytokines and chemoattractants. In models of inflammation in the living animal, the shedding of glycans and diminished thickness of the glycocalyx rapidly occur to facilitate penetration by the WBCs and adhesion to the EC. The primary effectors of glycan shedding appear to be metalloproteases and heparanase released by the EC. Retardation of glycan shedding and WBC-EC adhesion has been demonstrated in vivo using MMP inhibitors and low-molecular-weight heparin (LMWH), where the latter competitively binds to heparanase liberated by the EC. Together, these agents may serve to stabilize the ESL and provide a useful strategy for treatment of inflammatory disorders.
    MeSH term(s) Animals ; Cell Adhesion ; Endothelium, Vascular ; Glycocalyx ; Heparin, Low-Molecular-Weight ; Leukocytes/cytology
    Chemical Substances Heparin, Low-Molecular-Weight
    Language English
    Publishing date 2018-10-12
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-319-96445-4_3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Preface.

    Lipowsky, Herbert

    Biorheology

    2019  Volume 56, Issue 2-3, Page(s) 73–75

    MeSH term(s) Animals ; Endothelial Cells/physiology ; Glycocalyx/physiology ; Humans ; Neoplasms/physiopathology ; Rheology
    Language English
    Publishing date 2019-11-22
    Publishing country Netherlands
    Document type Introductory Journal Article
    ZDB-ID 82015-5
    ISSN 1878-5034 ; 0006-355X
    ISSN (online) 1878-5034
    ISSN 0006-355X
    DOI 10.3233/BIR-190233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: In vivo studies of blood rheology in the microcirculation in an in vitro world: Past, present and future.

    Lipowsky, Herbert H

    Biorheology

    2013  Volume 50, Issue 1-2, Page(s) 3–16

    MeSH term(s) Animals ; Awards and Prizes ; Blood Viscosity/physiology ; History, 20th Century ; History, 21st Century ; Humans ; Microcirculation/physiology ; Rheology/history ; Rheology/methods ; Rheology/trends
    Language English
    Publishing date 2013
    Publishing country Netherlands
    Document type Addresses ; Biography ; Historical Article ; Portraits ; Research Support, N.I.H., Extramural
    ZDB-ID 82015-5
    ISSN 1878-5034 ; 0006-355X
    ISSN (online) 1878-5034
    ISSN 0006-355X
    DOI 10.3233/BIR-130625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Preface.

    Shin, Sehyun / Lipowsky, Herbert H

    Biorheology

    2015  Volume 52, Issue 1-2, Page(s) 1–3

    Language English
    Publishing date 2015
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 82015-5
    ISSN 1878-5034 ; 0006-355X
    ISSN (online) 1878-5034
    ISSN 0006-355X
    DOI 10.3233/BIR-150668
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Inhibition of inflammation induced shedding of the endothelial glycocalyx with low molecular weight heparin.

    Lipowsky, Herbert H / Lescanic, Anne

    Microvascular research

    2017  Volume 112, Page(s) 72–78

    Abstract: The endothelial surface layer (ESL) consists of the endothelial cell (EC) glycocalyx and adsorbed proteins, and forms a barrier between blood and the EC. Enzymatic shedding of the ESL in response to cytokines may expose receptors for leukocyte (WBC) ... ...

    Abstract The endothelial surface layer (ESL) consists of the endothelial cell (EC) glycocalyx and adsorbed proteins, and forms a barrier between blood and the EC. Enzymatic shedding of the ESL in response to cytokines may expose receptors for leukocyte (WBC) adhesion and increase vascular permeability. Thus, intravital microscopy was used to explore stabilization of the ESL with low molecular weight heparin (LMWH) to mitigate structural changes with inflammation. Following bolus infusions (i.v.) of LMWH (0.12-1.6mg/kg), shedding of glycans in response to 10
    MeSH term(s) Animals ; Capillary Permeability/drug effects ; Cell Adhesion/drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Glycocalyx/drug effects ; Glycocalyx/metabolism ; Glycocalyx/pathology ; Heparin, Low-Molecular-Weight/pharmacology ; Inflammation/blood ; Inflammation/drug therapy ; Inflammation/metabolism ; Inflammation/pathology ; Intravital Microscopy ; Leukocytes/drug effects ; Leukocytes/metabolism ; Leukocytes/pathology ; Male ; Mesentery/blood supply ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Polysaccharides/metabolism ; Rats, Wistar ; Time Factors ; Venules/drug effects ; Venules/metabolism ; Venules/pathology
    Chemical Substances Heparin, Low-Molecular-Weight ; Polysaccharides ; N-Formylmethionine Leucyl-Phenylalanine (59880-97-6)
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80307-8
    ISSN 1095-9319 ; 0026-2862
    ISSN (online) 1095-9319
    ISSN 0026-2862
    DOI 10.1016/j.mvr.2017.03.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Preface.

    Lipowsky, Herbert H / Nash, Gerard

    Biorheology

    2015  Volume 52, Issue 5-6, Page(s) 293–294

    MeSH term(s) Bibliography as Topic ; Humans
    Language English
    Publishing date 2015
    Publishing country Netherlands
    Document type Introductory Journal Article
    ZDB-ID 82015-5
    ISSN 1878-5034 ; 0006-355X
    ISSN (online) 1878-5034
    ISSN 0006-355X
    DOI 10.3233/BIR-150674
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  9. Article: Protease Activity and the Role of the Endothelial Glycocalyx in Inflammation.

    Lipowsky, Herbert H

    Drug discovery today. Disease models

    2011  Volume 8, Issue 1, Page(s) 57–62

    Abstract: A new paradigm for governance of leukocyte-endothelium (WBC-EC) adhesion during the inflammatory process is presented in which shedding of the endothelial glycocalyx exposes adhesion molecules on the EC surface, which promotes WBC-EC adhesion. It is ... ...

    Abstract A new paradigm for governance of leukocyte-endothelium (WBC-EC) adhesion during the inflammatory process is presented in which shedding of the endothelial glycocalyx exposes adhesion molecules on the EC surface, which promotes WBC-EC adhesion. It is postulated that the effector of this shedding is the activation of extracellular proteases, one of which may be a member of the matrix metalloproteinase (MMP) family of zinc dependent endopetidases. This model for the role of the glycocalyx as a barrier to WBC-EC adhesion includes the additional participation of normally active extracellular proteolytic enzymes, i.e. sheddases, which may cleave proteoglycans or activate lyases that cleave GAG chains in the glycocalyx. In support of this hypothesis, studies are examined which have established the concurrent activation of MMP proenzymes on the EC surface, shedding of the glycocalyx, and enhanced WBC-EC adhesion.
    Language English
    Publishing date 2011-10-28
    Publishing country Netherlands
    Document type Journal Article
    ISSN 1740-6757
    ISSN 1740-6757
    DOI 10.1016/j.ddmod.2011.05.004
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  10. Article ; Online: The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases.

    Lipowsky, Herbert H

    Annals of biomedical engineering

    2011  Volume 40, Issue 4, Page(s) 840–848

    Abstract: The endothelial cell (EC) surface is coated with a layer of polysaccharides linked to membrane-bound and trans-membrane proteoglycans that comprise the glycocalyx, which is augmented by adsorbed proteins derived from the blood stream. This surface layer ... ...

    Abstract The endothelial cell (EC) surface is coated with a layer of polysaccharides linked to membrane-bound and trans-membrane proteoglycans that comprise the glycocalyx, which is augmented by adsorbed proteins derived from the blood stream. This surface layer has been shown to affect hemodynamics in small blood vessels of the microcirculation, the resistance to flow, and leukocyte (WBC) to EC adhesion. Parallel studies of WBC-EC adhesion in response to chemoattractants and cytokines, and shedding of constituents of the glycocalyx, have suggested a role for activation of extracellular proteases in mediating the dynamics of WBC adhesion in response to inflammatory and ischemic stimuli. Likely candidates among the many proteases present are the matrix metalloproteases (MMPs). Inhibition of MMP activation with sub-antimicrobial doses of doxycycline, or zinc chelators, has also inhibited WBC adhesion and shedding of glycans from the EC surface in response to the chemoattractant fMLP. Taken together, these studies suggest that shedding of the EC glycocalyx exposes adhesion receptors and thus enhances WBC-EC adhesion. Future therapeutic strategies for treating pathologies such as the low flow state and inflammation may benefit by further exploration of the mechanics of the glycocalyx in light of protease activation and shear-dependent effects.
    MeSH term(s) Animals ; Cell Adhesion/physiology ; Cell Adhesion Molecules/metabolism ; Cell Movement/drug effects ; Cell Movement/physiology ; Chemotactic Factors/metabolism ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Enzyme Activation/drug effects ; Enzyme Activation/physiology ; Glycocalyx/metabolism ; Humans ; Leukocytes/enzymology ; Matrix Metalloproteinases/metabolism ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Polysaccharides/metabolism
    Chemical Substances Cell Adhesion Molecules ; Chemotactic Factors ; Polysaccharides ; N-Formylmethionine Leucyl-Phenylalanine (59880-97-6) ; Matrix Metalloproteinases (EC 3.4.24.-)
    Language English
    Publishing date 2011-10-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 185984-5
    ISSN 1573-9686 ; 0191-5649 ; 0090-6964
    ISSN (online) 1573-9686
    ISSN 0191-5649 ; 0090-6964
    DOI 10.1007/s10439-011-0427-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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