Stiffness-Induced Endothelial DLC-1 Expression Forces Leukocyte Spreading through Stabilization of the ICAM-1 Adhesome

Schimmel, Lilian; Stoel, Miesje M. van der; Rianna, Carmela; Stalborch, Anne-Marieke D. van; Ligt, Aafke de; Hoogenboezem, Mark; Tol, Simon; Rijssel, Jos van; Szulcek, Robert; Bogaard, Harm Jan; Hofmann, Patrick; Boon, Reinier A.; Radmacher, Manfred; Waard, Vivian de; Huveneers, Stephan; Buul, Jaap D. van

doi:10.1016/j.celrep.2018.08.045

Cited by 37 publications

(34 citation statements)

References 34 publications

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“…Leukocyte integrins assume both selective and cohesive adhesion via binding to distinct endothelial adhesion receptors such as the intercellular adhesion molecule 1 (ICAM-1) [125]. More recently, van Buul and colleagues have demonstrated that endothelial stiffening helps stabilize ICAM-1 adhesome in order to promote leukocyte spreading [133]. Integrins increase the binding avidity to ligands, which correlates with endothelial cellular stiffness.…”

Section: Potential Role Of Endothelial Cellular Stiffness In Cell mentioning

confidence: 99%

The Functional Implications of Endothelial Gap Junctions and Cellular Mechanics in Vascular Angiogenesis

Okamoto

Usuda

Tanaka

et al. 2019

Cancers

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Angiogenesis—the sprouting and growth of new blood vessels from the existing vasculature—is an important contributor to tumor development, since it facilitates the supply of oxygen and nutrients to cancer cells. Endothelial cells are critically affected during the angiogenic process as their proliferation, motility, and morphology are modulated by pro-angiogenic and environmental factors associated with tumor tissues and cancer cells. Recent in vivo and in vitro studies have revealed that the gap junctions of endothelial cells also participate in the promotion of angiogenesis. Pro-angiogenic factors modulate gap junction function and connexin expression in endothelial cells, whereas endothelial connexins are involved in angiogenic tube formation and in the cell migration of endothelial cells. Several mechanisms, including gap junction function-dependent or -independent pathways, have been proposed. In particular, connexins might have the potential to regulate cell mechanics such as cell morphology, cell migration, and cellular stiffness that are dynamically changed during the angiogenic processes. Here, we review the implication for endothelial gap junctions and cellular mechanics in vascular angiogenesis.

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Section: Potential Role Of Endothelial Cellular Stiffness In Cell mentioning

confidence: 99%

The Functional Implications of Endothelial Gap Junctions and Cellular Mechanics in Vascular Angiogenesis

Okamoto

Usuda

Tanaka

et al. 2019

Cancers

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“…Thus, both artery and vein endothelial cellular stiffening upon exposure to proinflammatory stimuli may trigger leukocyte and monocyte adhesion at inflamed vascular regions. Several studies have shown that leukocyte adhesion and transendothelial migration are facilitated when in contact with stiff vascular vessels or substrates [40][41][42]. This is due to durotaxis, which is recognized as a cell migration property that leads to increased stiffness [43].…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Soluble Thrombomodulin Suppresses Monocyte Adhesion by Reducing Lipopolysaccharide-Induced Endothelial Cellular Stiffening

Okamoto

Kawamoto

Usuda

et al. 2020

Cells

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Endothelial cellular stiffening has been observed not only in inflamed cultured endothelial cells but also in the endothelium of atherosclerotic regions, which is an underlying cause of monocyte adhesion and accumulation. Although recombinant soluble thrombomodulin (rsTM) has been reported to suppress the inflammatory response of endothelial cells, its role in regulating endothelial cellular stiffness remains unclear. The purpose of this study was to investigate the impact of anticoagulant rsTM on lipopolysaccharide (LPS)-induced endothelial cellular stiffening. We show that LPS increases endothelial cellular stiffness by using atomic force microscopy and that rsTM reduces LPS-induced cellular stiffening not only through the attenuation of actin fiber and focal adhesion formation but also via the improvement of gap junction functionality. Moreover, post-administration of rsTM, after LPS stimulation, attenuated LPS-induced cellular stiffening. We also found that endothelial cells regulate leukocyte adhesion in a substrate- and cellular stiffness-dependent manner. Our result show that LPS-induced cellular stiffening enhances monocytic THP-1 cell line adhesion, whereas rsTM suppresses THP-1 cell adhesion to inflamed endothelial cells by reducing cellular stiffness. Endothelial cells increase cellular stiffness in reaction to inflammation, thereby promoting monocyte adhesion. Treatment of rsTM reduced LPS-induced cellular stiffening and suppressed monocyte adhesion in a cellular stiffness-dependent manner.

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“…Previous studies have demonstrated that stiff substrates reduce the tight junctions and enhance permeability of endothelial monolayers through mechanism involving Src, VE-cadherin and focal adhesions [16][17][18] . In addition, substrate stiffness regulates endothelial inflammation and leukocyte adhesion/transmigration [16][17][18][19] . Endothelial cells also alter their mechanical stiffness based on the substrate stiffness through a mechanism involving PKA and PECAM-1 20 .…”

Section: Substrate Compliance Regulates Sdc1 Tension and Binding To Cmentioning

confidence: 99%

Mechanical Tension in Syndecan-1 is Regulated by Extracellular Mechanical Cues and Fluidic Shear Stress

Lei

Voyvodic

et al. 2020

Preprint

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The endothelium plays a central role in regulating vascular homeostasis and is key in determining the response to materials implanted in the vascular system. Endothelial cells are uniquely sensitive to biophysical cues from applied forces and their local cellular microenvironment. The glycocalyx is a layer of proteoglycans, glycoproteins and glycosaminoglycans that lines the luminal surface of the vascular endothelium, interacting directly with the components of the blood and the forces of blood flow. In this work, we examined the changes in mechanical tension of syndecan-1, a cell surface proteoglycan that is an integral part of the glycocalyx, in response to substrate stiffness and fluidic shear stress. Our studies demonstrate that syndecan-1 is mechanically responsive to extracellular mechanical cues and alters its association with cytoskeletal and adhesion-related proteins in response to substrate stiffness and physiological flow.

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Stiffness-Induced Endothelial DLC-1 Expression Forces Leukocyte Spreading through Stabilization of the ICAM-1 Adhesome

Cited by 37 publications

References 34 publications

The Functional Implications of Endothelial Gap Junctions and Cellular Mechanics in Vascular Angiogenesis

The Functional Implications of Endothelial Gap Junctions and Cellular Mechanics in Vascular Angiogenesis

Recombinant Human Soluble Thrombomodulin Suppresses Monocyte Adhesion by Reducing Lipopolysaccharide-Induced Endothelial Cellular Stiffening

Mechanical Tension in Syndecan-1 is Regulated by Extracellular Mechanical Cues and Fluidic Shear Stress

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