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

PloS One
Ektoras HadjipanayiArndt F Schilling

Abstract

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...Continue Reading

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Citations

Nov 25, 2017·Advanced Healthcare Materials·Hwan D KimNathaniel S Hwang
Nov 27, 2019·Macromolecular Bioscience·Iwan Vaughan RobertsNicola Tirelli
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Oct 28, 2019·ACS Biomaterials Science & Engineering·Carly A JosephRupak M Rajachar

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Methods Mentioned

BETA
reverse phase chromatography
acetylation
Profiler
ELISA
fluorescence microscopy

Software Mentioned

MaxQuant
Image J
SensorDish Reader
SPSS
Andromeda

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