Print Email Facebook Twitter Molecular weight fibrinogen variants determine angiogenesis rate in a fibrin matrix in vitro and in vivo Title Molecular weight fibrinogen variants determine angiogenesis rate in a fibrin matrix in vitro and in vivo Author Kaijzel, E.L. Koolwijk, P. van Erck, M.G.M. van Hinsbergh, V.W.M. de Maat, M.P.M. TNO Kwaliteit van Leven Publication year 2006 Abstract Background: During wound repair, fibrin acts both as a barrier to prevent blood loss and as a temporary matrix for the invasion and ingrowth of endothelial and tissue cells. A well-controlled angiogenesis process in the fibrinous exudate matrix is crucial for optimal wound healing. The composition and structure of the fibrin matrix are important determinants of the invasion of endothelial cells and capillary-tube formation into the matrix. Objective: Fibrinogen circulates in a high and low molecular weight form (HMW and LMW, respectively) and the purpose of this study was to investigate how fibrin matrices from these naturally occurring fibrinogen variants influence angiogenesis. Angiogenesis was studied using an in vitro model in which human microvascular endothelial cells (hMVEC) were cultured on three-dimensional fibrin matrices from different fibrinogen forms, and using two in vivo mouse models. Results: The in vitro angiogenesis in an HMW-fibrin matrix shows increased cell and tubular structure ingrowth compared with unfractionated fibrin matrix (median increase 58%, range 46-234%). The ingrowth of tubular structures in an LMW-fibrin matrices is decreased when compared with unfractionated fibrin (median decrease 70%, range 67-100%). Similar results were observed for in vivo angiogenesis. Conclusions: The naturally occurring fibrinogen variants HMW- and LMW-fibrin modulate the angiogenic capacity of endothelial cells in fibrin matrices. The different effects of the molecular weight fibrinogen variants provide further insight in the matrix characteristics in angiogenesis and could possibly be applied in the context of tissue engineering and wound healing. © 2006 International Society on Thrombosis and Haemostasis. Subject BiologyBiomedical ResearchAngiogenesisEndothelial cellsFibrin matrixFibrinogen variantsTissue engineeringWound healingFibrinFibrinogen variantAngiogenesisAnimal cellAnimal experimentAnimal modelCell functionControlled studyEndothelium cellFibrin formationGrowth rateHumanHuman cellHuman cell cultureIn vitro studyIn vivo studyMicrovasculatureMolecular weightMouseNonhumanPriority journalProtein determinationProtein functionProtein structureRegulatory mechanismStructure analysisAnimalsCell MovementCells, CulturedEndothelial CellsFemaleFibrinFibrinogenHumansKineticsMiceMice, Inbred StrainsMicroscopy, Electron, ScanningMolecular WeightNeovascularization, PhysiologicWound Healing To reference this document use: http://resolver.tudelft.nl/uuid:a56b68aa-982d-41cf-8343-705e33950842 DOI https://doi.org/10.1111/j.1538-7836.2006.02081.x TNO identifier 239459 ISSN 1538-7933 Source Journal of Thrombosis and Haemostasis, 4 (9), 1975-1981 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.