Molecular weight fibrinogen variants alter gene expression and functional characteristics of human endothelial cells

Weijers, Ester M.; Wijhe, Michiel H. van; Joosten, Leo A. B.; Horrevoets, Anton J.G.; Maat, Moniek P.M. de; Hinsbergh, Victor W.M. van; Koolwijk, Pieter

doi:10.1111/j.1538-7836.2010.04096.x

Cited by 21 publications

(23 citation statements)

References 46 publications

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“…A matrix composed of only LMW fibrinogen has thinner fibers and has a denser structure than a matrix made from only HMW fibrinogen (Figure 7). Small differences in fibrin matrix lead to different gene expression patterns in endothelial cells [47] and influence tube formation [18]. Tube formation was more extensive in HMW than in LMW matrices.…”

Section: Matrix Degradation and Sprout Morphologymentioning

confidence: 97%

“…Endothelial cells secrete MMPs (matrix metalloproteinases) to degrade the basement membrane. The production and activity of u-PA and MMPs is interlinked; u-PA activity is suggested to induce MMP activity indirectly and at least one membrane-bound MMP (MT1-MMP) is known to be capable of fibrin degradation as well [47]. Proteolytic activity can be manipulated by stimulation the cells with angiogenic factors or inflammatory factors [8].…”

Section: Matrix Degradation and Sprout Morphologymentioning

confidence: 99%

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Computational Modeling of Angiogenesis: Towards a Multi-Scale Understanding of Cell–Cell and Cell–Matrix Interactions

Boas

Palm

Koolwijk

et al. 2012

Mechanical and Chemical Signaling in Angiogenesis

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Combined with in vitro and in vivo experiments, mathematical and computational modeling are key to unraveling how mechanical and chemical signaling by endothelial cells coordinates their organization into capillary-like tubes. While in vitro and in vivo experiments can unveil the effects of for example environmental changes or gene knockouts, computational models provide a way to formalize and understand the mechanisms underlying these observations. This chapter reviews recent computational approaches to model angiogenesis, and discusses the insights they provide in the mechanisms of angiogenesis. We introduce a new cell-based computational model of an in vitro assay of angiogenic sprouting from endothelial monolayers in fibrin matrices. Endothelial cells are modeled by the Cellular Potts Model, combined with continuum descriptions to model haptotaxis and proteolysis of the extracellular matrix. The computational model demonstrates how a variety of cellular structural properties and behaviors determine the dynamics of tube formation. We aim to extend this model to a multi- * these authors contributed equally to this work scale model in the sense that cells, extracellular matrix and cell-regulation are described at different levels of detail and feedback on each other. Finally we discuss how computational modeling, combined with in vitro and in vivo modeling steers experiments, and how it generates new experimental hypotheses and insights on the mechanics of angiogenesis.

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Section: Matrix Degradation and Sprout Morphologymentioning

confidence: 97%

Section: Matrix Degradation and Sprout Morphologymentioning

confidence: 99%

Computational Modeling of Angiogenesis: Towards a Multi-Scale Understanding of Cell–Cell and Cell–Matrix Interactions

Boas

Palm

Koolwijk

et al. 2012

Mechanical and Chemical Signaling in Angiogenesis

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“…13 Human umbilical vein endothelial cells (HUVECs) 17,18 were seeded on these fibrinogen coatings to determine their adhesion, migration, and proliferation and compared with a placebo coating of 1% gelatin. Coating of fibrinogen to plastic results in a fibrin-like structure.…”

Section: Fibrinogen Coatingsmentioning

confidence: 99%

“…The fibrin matrix facilitates cell adhesion, migration, and proliferation and thus stimulates angiogenesis. 12,13 Further, fibrin binds growth factors that influence these processes, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2).…”

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confidence: 99%

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Specific Effects of Fibrinogen and the γA and γ′-Chain Fibrinogen Variants on Angiogenesis and Wound Healing

Cheung

Weijers²,

Tuk³

et al. 2015

Tissue Engineering Part A

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In a newly formed wound, the natural fibrin network provides the first temporary matrix for tissue repair. Topical application of fibrin to a new wound may improve wound healing. A matrix of the common natural g¢ fibrin variant may further improve wound healing because it is expected to have a different architecture and this will influence angiogenesis, because it possesses increased thrombin and factor XIII binding and decreased platelet binding, when compared with the common gA fibrin matrix. Our objective was to determine the effect of fibrinogen and its gA and g¢ variants on angiogenesis and wound healing. We used in vitro angiogenesis models and an in vivo rat full-thickness excisional wound healing model. When comparing gA and g¢ fibrin in vitro, more tube-like structures were formed on day 7 in gA fibrin than in g¢ fibrin (13.83 -6.12 AU vs. 6.1 -1.46 AU). Wounds treated with fibrin demonstrated improved healing in vivo with more perfusion (47% -3% vs. 26% -4%, p < 0.01 in placebo) and higher CD34 density score (2.0 -0.4 vs. 2.8 -0.1, p < 0.01) on day 21 with fibrin matrices when compared with placebo-treated wounds. Increased perfusion was observed in gA fibrin-treated wounds on day 21 (53% -10% vs. 41% -7% for g¢ fibrin). The other parameters showed slightly improved (not significant) wound healing with gA fibrin compared with g¢ fibrin matrices. In conclusion, the use of fibrin and fibrin variant matrices offers an interesting methodology to stimulate the wound healing process.

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Vascular tissue construction on poly(ε-caprolactone) scaffolds by dynamic endothelial cell seeding: effect of pore size

Mathews

Colombus

Krishnan

et al. 2011

J Tissue Eng Regen Med

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In vitro tissue engineering for fabrication of small diameter vascular grafts probably undergoes a sequence of events similar to the in vivo angiogenesis process. In both cases endothelial cells (ECs) play the crucial role in generating a non-thrombogenic vessel lumen and stabilization of ECs in the lumen of new vessels requires the deposition of collagen IV and elastin. Shear stress is an important in vivo signal for inducing synthesis of extracellular matrix (ECM) components, collagen IV and elastin, which form the basement membrane in the case of new blood vessels. Stimulation of ECs may therefore produce collagen and elastin in the lumen of a polymeric scaffold during the vascular tissue-engineering process if appropriate biochemical and mechanical signals are presented. However, the morphology and physicochemical characteristics of polymer scaffolds may also be crucial for EC monolayer formation and ECM deposition. In this study, tubular scaffolds made of biodegradable poly(ε-caprolactone) (PCL) with biomimetic fibrin-based coating were evaluated to compare the effects of pore sizes on surface coverage of ECs and synthesis of ECM under dynamic culture conditions. Actin was stained for identification of cells, while specific antibodies were used for locating collagen IV and elastin deposition on the scaffolds. It was found that dynamic seeding of ECs in the lumen stabilized the cells and aligned them along the direction of flow, with better deposition of insoluble elastin and collagen IV when ∼75% of pores were < 24 µm in diameter. In addition, monolayer on the ε-PCL scaffolds with lower pore sizes was found to produce nitric oxide (NO), indicating a non-thrombogenic EC layer in the lumen.

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Molecular weight fibrinogen variants alter gene expression and functional characteristics of human endothelial cells

Cited by 21 publications

References 46 publications

Computational Modeling of Angiogenesis: Towards a Multi-Scale Understanding of Cell–Cell and Cell–Matrix Interactions

Computational Modeling of Angiogenesis: Towards a Multi-Scale Understanding of Cell–Cell and Cell–Matrix Interactions

Specific Effects of Fibrinogen and the γA and γ′-Chain Fibrinogen Variants on Angiogenesis and Wound Healing

Vascular tissue construction on poly(ε-caprolactone) scaffolds by dynamic endothelial cell seeding: effect of pore size

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