Mechano‐sensing and transduction by endothelial surface glycocalyx: composition, structure, and function

Fu, Bingmei M.; Tarbell, John M.

doi:10.1002/wsbm.1211

Cited by 149 publications

(141 citation statements)

References 60 publications

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“…Secondly, it is well established that the GCX provides a protective surface on ECs that suppresses leucocyte adhesion and associated inflammation, supports the vascular transport barrier and mediates critical mechanotransduction processes such as flow-mediated vasodilation [1][2][3][4]. It is only beginning to be recognized that the GCX plays an important role in vascular diseases.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

“…The chemical composition, mechanical characteristics and multiple physiological functions of this layer on vascular endothelial cells (ECs) have been described extensively in several recent papers [1][2][3][4] and will not be the focus of the present review. Instead, we will consider the GCX on many other cell types including cancer cells.…”

Section: Introduction and Overviewmentioning

confidence: 99%

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The glycocalyx and its significance in human medicine

2016

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Cells are covered by a surface layer of glycans that is referred to as the 'glycocalyx'. In this review, we focus on the role of the glycocalyx in vascular diseases (atherosclerosis, stroke, hypertension, kidney disease and sepsis) and cancer. The glycocalyx and its principal glycosaminoglycans [heparan sulphate (HS) and hyaluronic acid (HA)] and core proteins (syndecans and glypicans) are degraded in vascular diseases, leading to a breakdown of the vascular permeability barrier, enhanced access of leucocytes to the arterial intima that propagate inflammation and alteration of endothelial mechanotransduction mechanisms that protect against disease. By contrast, the glycocalyx on cancer cells is generally robust, promoting integrin clustering and growth factor signalling, and mechanotransduction of interstitial flow shear stress that is elevated in tumours to upregulate matrix metalloproteinase release which enhances cell motility and metastasis. HS and HA are consistently elevated on cancer cells and are associated with tumour growth and metastasis. Later, we will review the agents that might be used to enhance or protect the glycocalyx to combat vascular disease, as well as a different set of compounds that can degrade the cancer cell glycocalyx to suppress cell growth and metastasis. It is clear that what is beneficial for either vascular disease or cancer will not be so for the other. The overarching conclusions are that (i) the importance of the glycocalyx in human medicine is only beginning to be recognized, and (ii) more detailed studies of glycocalyx involvement in vascular diseases and cancer will lead to novel treatment modalities.

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Section: Summary and Future Directionsmentioning

confidence: 99%

Section: Introduction and Overviewmentioning

confidence: 99%

The glycocalyx and its significance in human medicine

2016

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“…While traditional consideration of the endothelium is that it represents the interface between circulating blood and the vascular smooth muscle, the surface of EC is decorated with a layer called the glycocalyx that contributes to EC integrity, mechanotransduction, leukocyte adherence, and coordination of EC signaling (van den Berg et al, 2006;Reitsma et al, 2007;Fu and Tarbell, 2013). This cell-free layer, ranging from 0.5 to 4.5 mm in thickness depending on the vessel, is composed of a multitude of proteoglycans and glycoproteins that make it a relatively viscous layer that protects the endothelium from changes in shear stress and pressure, but also from undue leukocyte and platelet adherence and sequestration of NO by hemoglobin (Brouland et al, 1999;Gao and Lipowsky, 2010;Hightower et al, 2011).…”

Section: The Glycocalyx Mechanosensation and Mechanotransductionmentioning

confidence: 99%

The Biochemistry of Endothelial Cells

Savani

2015

Comparative Biology of the Normal Lung

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“…"Triggers" of mechanical sensing seem to center on tissues with unique anatomic relationships with each other rather than activation of specific chemical receptor macromolecules in single cells. [14][15][16][17][18][19] Low Intensity, Alternating Electrical Currents: Are There Specific "Triggers" for AC Effects on Cells?…”

Section: Non-ionizing and Ionizing Electromagnetic Irradiationmentioning

confidence: 99%

Coupling of physical characteristics of non-ionizing irradiation to specific mechanisms of cell death: are we there yet?

Thomsen¹

2015

Energy-Based Treatment of Tissue and Assessment VIII

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The recent discovery of the various specific" triggers" and mechanisms of cell life and death responses suggests that certain non-ionizing irradiation spectra and other physical signals could be coupled with specific cellular "triggers" to improve diagnostic or treatment effects. Genetic, chemical and/or physical modifications of specific extrinsic cellular "triggers" have centered on chemical binding of specific molecules to specific receptors, i.e. chemical " triggers" thus allowing development of specific drugs to counteract the initiating function of the "triggers" in single cells. Investigations of non-ionizing irradiation effects on cells and tissues indicate that their "triggers" involve intimate interactions of linked components of the extracellular matrix and the cytoskeleton in tissues. Therefore, the search for single "triggers" that may work well for chemical "triggers" in single cells in culture may not be effective for discovery of the mechanisms that initiate sensing of the stimulations of non-ionizing irradiation and mechanical force.In cell biology, the mechanisms of life and death usually involve a series of complex, chemical, mechanical and/or electrical events that are highly interactive with many other physiological and pathological mechanisms within and outside the cell. To distinguish one event from any of the others the following things have to be established:1. Precise description of the ultimate cellular response to be studied i.e. cell death, cell movement, energy production, protein synthesis, cell division, etc. The definitions of these responses could and should be refined as an investigator finds out more information about the events in his studies. For example, cell death could be due to apoptosis (identified by production of apoptotic bodies) therefore future studies could be focused on finding markers of the extrinsic or intrinsic apoptotic pathways.2. Identification of a specific act or " triggered" reaction that initiates a series of events which produces the cellular response to be studied. For example, apoptosis can be "triggered" by ligand binding of tumor necrosis factor (TNF) to the "death receptor" found on the surfaces of certain cells.3. "Markers" are the key substance(s) or reaction(s) that distinguish a specific series of events. The series can produce several markers along the way. For instance, a key marker of apoptosis is the production of caspase 8.4. Identification of "end points", the results or cellular responses of the series of events or a subset of events. These are frequently are measureable thus useful for mathematical modeling. Ultimate cell responses such as cell death are "endpoints" but other well-defined products or reactions found within the series of events, such as caspase 8 production which occurs early in apoptosis also can be designated as desired endpoints of study. Keynote Paper Energy-based Treatment of Tissue and Assessment VIII, edited by Thomas P. Ryan Proc. of SPIE Vol. 9326, 932603 · © 2015 SPIE · CCC code: 1605-7422/15/$18

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Mechano‐sensing and transduction by endothelial surface glycocalyx: composition, structure, and function

Cited by 149 publications

References 60 publications

The glycocalyx and its significance in human medicine

The glycocalyx and its significance in human medicine

The Biochemistry of Endothelial Cells

Coupling of physical characteristics of non-ionizing irradiation to specific mechanisms of cell death: are we there yet?

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