A Bilayered, Electrospun Poly(Glycerol-Sebacate)/Polyurethane-Polyurethane Scaffold for Engineering of Endothelial Basement Membrane

The endothelial cell basement membrane (BM) is a barrier to migrating leukocytes and a rich source of signaling molecules that can influence extravasating cells. Using mice lacking the major endothelial BM components, laminin 411 or 511, in murine experimental autoimmune encephalomyelitis (EAE), we show here that loss of endothelial laminin 511 results in enhanced disease severity due to increased T cell infiltration and altered polarization and pathogenicity of infiltrating T cells. In vitro adhesion and migration assays reveal higher binding to laminin 511 than laminin 411 but faster migration across laminin 411. In vivo and in vitro analyses suggest that integrin α6β1- and αvβ1-mediated binding to laminin 511–high sites not only holds T cells at such sites but also limits their differentiation to pathogenic Th17 cells. This highlights the importance of the interface between the endothelial monolayer and the underlying BM for modulation of immune cell phenotype.

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Flow-induced Reorganization of Laminin-integrin Networks Within the Endothelial Basement Membrane Uncovered by Proteomics

Molecular & Cellular Proteomics ◽

10.1074/mcp.ra120.001964 ◽

2020 ◽

Vol 19 (7) ◽

pp. 1179-1192 ◽

Cited By ~ 3

Author(s):

Eelke P. Béguin ◽

Esmée F. J. Janssen ◽

Mark Hoogenboezem ◽

Alexander B. Meijer ◽

Arie J. Hoogendijk ◽

...

Keyword(s):

Blood Flow ◽

Basement Membrane ◽

Cell Surface ◽

Signaling Pathways ◽

Surface Proteins ◽

Chemical Labeling ◽

Hemodynamic Forces ◽

Endothelial Basement Membrane ◽

Factor Α ◽

Flow Exposure

The vessel wall is continuously exposed to hemodynamic forces generated by blood flow. Endothelial mechanosensors perceive and translate mechanical signals via cellular signaling pathways into biological processes that control endothelial development, phenotype and function. To assess the hemodynamic effects on the endothelium on a system-wide level, we applied a quantitative mass spectrometry approach combined with cell surface chemical footprinting. SILAC-labeled endothelial cells were subjected to flow-induced shear stress for 0, 24 or 48 h, followed by chemical labeling of surface proteins using a non-membrane permeable biotin label, and analysis of the whole proteome and the cell surface proteome by LC-MS/MS analysis. These studies revealed that of the >5000 quantified proteins 104 were altered, which were highly enriched for extracellular matrix proteins and proteins involved in cell-matrix adhesion. Cell surface proteomics indicated that LAMA4 was proteolytically processed upon flow-exposure, which corresponded to the decreased LAMA4 mass observed on immunoblot. Immunofluorescence microscopy studies highlighted that the endothelial basement membrane was drastically remodeled upon flow exposure. We observed a network-like pattern of LAMA4 and LAMA5, which corresponded to the localization of laminin-adhesion molecules ITGA6 and ITGB4. Furthermore, the adaptation to flow-exposure did not affect the inflammatory response to tumor necrosis factor α, indicating that inflammation and flow trigger fundamentally distinct endothelial signaling pathways with limited reciprocity and synergy. Taken together, this study uncovers the blood flow-induced remodeling of the basement membrane and stresses the importance of the subendothelial basement membrane in vascular homeostasis.

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Endothelial cells interact with the core protein of basement membrane perlecan through beta 1 and beta 3 integrins: an adhesion modulated by glycosaminoglycan.

The Journal of Cell Biology ◽

10.1083/jcb.119.4.945 ◽

1992 ◽

Vol 119 (4) ◽

pp. 945-959 ◽

Cited By ~ 131

Author(s):

K Hayashi ◽

J A Madri ◽

P D Yurchenco

Keyword(s):

Endothelial Cells ◽

Cell Adhesion ◽

Basement Membrane ◽

Core Protein ◽

Affinity Column ◽

Heparin Binding ◽

The Core ◽

Heparan Sulfates ◽

Domain Iii ◽

Endothelial Basement Membrane

Aortic endothelial cells adhere to the core protein of murine perlecan, a heparan sulfate proteoglycan present in endothelial basement membrane. We found that cell adhesion was partially inhibited by beta 1 integrin-specific mAb and almost completely blocked by a mixture of beta 1 and alpha v beta 3 antibodies. Furthermore, adhesion was partially inhibited by a synthetic peptide containing the perlecan domain III sequence LPASFRGDKVTSY (c-RGD) as well as by GRGDSP, but not by GRGESP. Both antibodies contributed to the inhibition of cell adhesion to immobilized c-RGD whereas only beta 1-specific antibody blocked residual cell adhesion to proteoglycan core in the presence of maximally inhibiting concentrations of soluble RGD peptide. A fraction of endothelial surface-labeled detergent lysate bound to a core affinity column and 147-, 116-, and 85-kD proteins were eluted with NaCl and EDTA. Polyclonal anti-beta 1 and anti-beta 3 integrin antibodies immunoprecipitated 116/147 and 85/147 kD surface-labeled complexes, respectively. Cell adhesion to perlecan was low compared to perlecan core, and cell adhesion to core, but not to immobilized c-RGD, was selectively inhibited by soluble heparin and heparan sulfates. This inhibition by heparin was also observed with laminin and fibronectin and, in the case of perlecan, was found to be independent of heparin binding to substrate. These data support the hypothesis that endothelial cells interact with the core protein of perlecan through beta 1 and beta 3 integrins, that this binding is partially RGD-independent, and that this interaction is selectively sensitive to a cell-mediated effect of heparin/heparan sulfates which may act as regulatory ligands.

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Endothelial basement membrane and seamless-type endothelium in the repair process of cerebral infarction in rats

Virchows Archiv A Pathological Anatomy and Histopathology ◽

10.1007/bf00718621 ◽

1989 ◽

Vol 414 (5) ◽

pp. 385-392 ◽

Cited By ~ 10

Author(s):

Yasuji Yoshida ◽

Mitsunori Yamada ◽

Koichi Wakabayashi ◽

Fusahiro Ikuta ◽

Toshiro Kumanishi

Keyword(s):

Basement Membrane ◽

Cerebral Infarction ◽

Repair Process ◽

Endothelial Basement Membrane

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Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation

Blood ◽

10.1182/blood-2009-05-222364 ◽

2009 ◽

Vol 114 (24) ◽

pp. 5091-5101 ◽

Cited By ~ 339

Author(s):

Amber N. Stratman ◽

Kristine M. Malotte ◽

Rachel D. Mahan ◽

Michael J. Davis ◽

George E. Davis

Keyword(s):

Basement Membrane ◽

Tube Formation ◽

Tissue Inhibitor Of Metalloproteinase ◽

Collagen Type Iv ◽

Matrix Assembly ◽

Matrix Deposition ◽

Vascular Basement Membrane ◽

Membrane Matrix ◽

Type Iv ◽

Endothelial Basement Membrane

AbstractWe show that endothelial cell (EC)–generated vascular guidance tunnels (ie, matrix spaces created during tube formation) serve as conduits for the recruitment and motility of pericytes along EC ablumenal surfaces to facilitate vessel maturation events, including vascular basement membrane matrix assembly and restriction of EC tube diameter. During quail development, pericyte recruitment along microvascular tubes directly correlates with vascular basement membrane matrix deposition. Pericyte recruitment to EC tubes leads to specific induction of fibronectin and nidogen-1 (ie, matrix-bridging proteins that link together basement membrane components) as well as perlecan and laminin isoforms. Coincident with these events, up-regulation of integrins, α5β1, α3β1, α6β1, and α1β1, which bind fibronectin, nidogens, laminin isoforms, and collagen type IV, occurs in EC-pericyte cocultures, but not EC-only cultures. Integrin-blocking antibodies to these receptors, disruption of fibronectin matrix assembly, and small interfering RNA suppression of pericyte tissue inhibitor of metalloproteinase (TIMP)-3 (a known regulator of vascular tube stabilization) all lead to decreased EC basement membrane, resulting in increased vessel lumen diameter, a key indicator of dysfunctional EC-pericyte interactions. Thus, pericyte recruitment to EC-lined tubes during vasculogenesis is a stimulatory event controlling vascular basement membrane matrix assembly, a fundamental maturation step regulating the transition from vascular morphogenesis to stabilization.

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CCN2/Connective Tissue Growth Factor Is Essential for Pericyte Adhesion and Endothelial Basement Membrane Formation during Angiogenesis

PLoS ONE ◽

10.1371/journal.pone.0030562 ◽

2012 ◽

Vol 7 (2) ◽

pp. e30562 ◽

Cited By ~ 81

Author(s):

Faith Hall-Glenn ◽

R. Andrea De Young ◽

Bau-Lin Huang ◽

Ben van Handel ◽

Jennifer J. Hofmann ◽

...

Keyword(s):

Growth Factor ◽

Connective Tissue ◽

Basement Membrane ◽

Connective Tissue Growth Factor ◽

Tissue Growth ◽

Membrane Formation ◽

Endothelial Basement Membrane

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Endothelial basement membrane laminin 511 is essential for shear stress response

The EMBO Journal ◽

10.15252/embj.201694756 ◽

2016 ◽

Vol 36 (2) ◽

pp. 183-201 ◽

Cited By ~ 21

Author(s):

Jacopo Di Russo ◽

Anna‐Liisa Luik ◽

Lema Yousif ◽

Sigmund Budny ◽

Hans Oberleithner ◽

...

Keyword(s):

Shear Stress ◽

Stress Response ◽

Basement Membrane ◽

Endothelial Basement Membrane ◽

Shear Stress Response

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Designing Cardiovascular Implants Taking in View the Endothelial Basement Membrane

International Journal of Molecular Sciences ◽

10.3390/ijms222313120 ◽

2021 ◽

Vol 22 (23) ◽

pp. 13120

Author(s):

Skadi Lau ◽

Manfred Gossen ◽

Andreas Lendlein

Keyword(s):

Basement Membrane ◽

Cell Types ◽

Adjacent Cell ◽

Design Strategies ◽

Graft Thrombosis ◽

Future Design ◽

Early Graft ◽

Endothelial Basement Membrane

Insufficient endothelialization of cardiovascular grafts is a major hurdle in vascular surgery and regenerative medicine, bearing a risk for early graft thrombosis. Neither of the numerous strategies pursued to solve these problems were conclusive. Endothelialization is regulated by the endothelial basement membrane (EBM), a highly specialized part of the vascular extracellular matrix. Thus, a detailed understanding of the structure–function interrelations of the EBM components is fundamental for designing biomimetic materials aiming to mimic EBM functions. In this review, a detailed description of the structure and functions of the EBM are provided, including the luminal and abluminal interactions with adjacent cell types, such as vascular smooth muscle cells. Moreover, in vivo as well as in vitro strategies to build or renew EBM are summarized and critically discussed. The spectrum of methods includes vessel decellularization and implant biofunctionalization strategies as well as tissue engineering-based approaches and bioprinting. Finally, the limitations of these methods are highlighted, and future directions are suggested to help improve future design strategies for EBM-inspired materials in the cardiovascular field.

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The Morphology of the Pecten Oculi and the Conus Papillaris

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100597 ◽

1968 ◽

Vol 26 ◽

pp. 170-171

Author(s):

R. F. Dunn

Keyword(s):

Basement Membrane ◽

Pigment Cell ◽

Pigment Cells ◽

Capillary Endothelium ◽

House Finch ◽

Osmiophilic Granules ◽

Pecten Oculi ◽

Tissue Space ◽

Endothelial Basement Membrane ◽

Connective Tissue Space

In this study, the pecten of the house finch, and the conus of the gecko, Eublipharis, were utilized. The structure of the house finch pecten resembled that of the pigeon. The capillary endothelium is characterized by an extensive luminal and abluminal system of plasma membrane plications (Fig. 1, LP and AP). The luminal ridges vary in length from 1.3 - 2.9μ, and are 40-90 mμ in width. The luminal and abluminal plications are separated by the narrow, rather dense endothelial cytoplasm which contains free ribosomes and dense mitochondria in addition to granular cytomembranes. The abluminal ridges are generally shorter, and rest on a basement membrane. Many of the pecten surface capillaries are separated from the vitreous by only a short distance of about 1μ. In other regions the capillaries are surrounded by pigmented cells, which contain smooth surfaced, very osmiophilic granules up to 1.6μ in diameter, a few smaller, irregularly shaped granules and the usual compliment of cytoplasmic organelles (Fig. 2).In sharp contrast to the pecten, the endothelium of the conus is relatively smooth and lacks any surface foldings as well as any fenestrations (Fig. 3). The endothelial basement membrane is separated from that of the pigment cell by a variable extracellular connective tissue space containing many collagen fibrils. The pigment cells contain melanin granules similar to those of the pecten (Fig.4).

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