The Fibrin Matrix Regulates Angiogenic Responses within the Hemostatic Microenvironment through Biochemical Control.

Autor:	Hadjipanayi E; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany; Department of Plastic, Reconstructive, Hand and Burn Surgery, Bogenhausen Hospital, 81925, Munich, Germany., Kuhn PH; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Neuroproteomics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany., Moog P; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany., Bauer AT; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany., Kuekrek H; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany., Mirzoyan L; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany., Hummel A; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany., Kirchhoff K; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany., Salgin B; Department of General Paediatrics, Neonatology and Paediatric Cardiology, University Children's Hospital Düsseldorf, 40225, Düsseldorf, Germany; Cambridge University Department of Paediatrics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom., Isenburg S; Department of Plastic, Reconstructive, Hand and Burn Surgery, Bogenhausen Hospital, 81925, Munich, Germany., Dornseifer U; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany; Department of Plastic, Reconstructive, Hand and Burn Surgery, Bogenhausen Hospital, 81925, Munich, Germany., Ninkovic M; Department of Plastic, Reconstructive, Hand and Burn Surgery, Bogenhausen Hospital, 81925, Munich, Germany., Machens HG; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany., Schilling AF; Department of Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universität München, D-81675, Munich, Germany; Center for Applied New Technologies in Engineering for Regenerative Medicine (Canter), Munich, Germany.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2015 Aug 28; Vol. 10 (8), pp. e0135618. Date of Electronic Publication: 2015 Aug 28 (Print Publication: 2015).
DOI:	10.1371/journal.pone.0135618
Abstrakt:	Conceptually, premature initiation of post-wound angiogenesis could interfere with hemostasis, as it relies on fibrinolysis. The mechanisms facilitating orchestration of these events remain poorly understood, however, likely due to limitations in discerning the individual contribution of cells and extracellular matrix. Here, we designed an in vitro Hemostatic-Components-Model (HCM) to investigate the role of the fibrin matrix as protein factor-carrier, independent of its cell-scaffold function. After characterizing the proteomic profile of HCM-harvested matrix releasates, we demonstrate that the key pro-/anti-angiogenic factors, VEGF and PF4, are differentially bound by the matrix. Changing matrix fibrin mass consequently alters the balance of releasate factor concentrations, with differential effects on basic endothelial cell (EC) behaviors. While increasing mass, and releasate VEGF levels, promoted EC chemotactic migration, it progressively inhibited tube formation, a response that was dependent on PF4. These results indicate that the clot's matrix component initially serves as biochemical anti-angiogenic barrier, suggesting that post-hemostatic angiogenesis follows fibrinolysis-mediated angiogenic disinhibition. Beyond their significance towards understanding the spatiotemporal regulation of wound healing, our findings could inform the study of other pathophysiological processes in which coagulation and angiogenesis are prominent features, such as cardiovascular and malignant disease.
Databáze:	MEDLINE
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