@article{Ishihara:2019:10.1182/blood.2019000510,
author = {Ishihara, J and Ishihara, A and Starke, RD and Peghaire, CR and Smith, KE and McKinnon, TAJ and Tabata, Y and Sasaki, K and White, MJV and Fukunaga, K and Laffan, MA and Lutolf, MP and Randi, AM and Hubbell, JA},
doi = {10.1182/blood.2019000510},
journal = {Blood},
pages = {2559--2569},
title = {The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing},
url = {http://dx.doi.org/10.1182/blood.2019000510},
volume = {133},
year = {2019}
}

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TY  - JOUR
AB  - During wound healing, the distribution, availability, and signaling of growth factors (GFs) are orchestrated by their binding to extracellular matrix components in the wound microenvironment. Extracellular matrix proteins have been shown to modulate angiogenesis and promote wound healing through GF binding. The hemostatic protein von Willebrand factor (VWF) released by endothelial cells (ECs) in plasma and in the subendothelial matrix has been shown to regulate angiogenesis; this function is relevant to patients in whom VWF deficiency or dysfunction is associated with vascular malformations. Here, we show that VWF deficiency in mice causes delayed wound healing accompanied by decreased angiogenesis and decreased amounts of angiogenic GFs in the wound. We show that in vitro VWF binds to several GFs, including vascular endothelial growth factor-A (VEGF-A) isoforms and platelet-derived growth factor-BB (PDGF-BB), mainly through the heparin-binding domain (HBD) within the VWF A1 domain. VWF also binds to VEGF-A and fibroblast growth factor-2 (FGF-2) in human plasma and colocalizes with VEGF-A in ECs. Incorporation of the VWF A1 HBD into fibrin matrices enables sequestration and slow release of incorporated GFs. In vivo, VWF A1 HBD-functionalized fibrin matrices increased angiogenesis and GF retention in VWF-deficient mice. Treatment of chronic skin wounds in diabetic mice with VEGF-A165 and PDGF-BB incorporated within VWF A1 HBD-functionalized fibrin matrices accelerated wound healing, with increased angiogenesis and smooth muscle cell proliferation. Therefore, the VWF A1 HBD can function as a GF reservoir, leading to effective angiogenesis and tissue regeneration.
AU  - Ishihara,J
AU  - Ishihara,A
AU  - Starke,RD
AU  - Peghaire,CR
AU  - Smith,KE
AU  - McKinnon,TAJ
AU  - Tabata,Y
AU  - Sasaki,K
AU  - White,MJV
AU  - Fukunaga,K
AU  - Laffan,MA
AU  - Lutolf,MP
AU  - Randi,AM
AU  - Hubbell,JA
DO  - 10.1182/blood.2019000510
EP  - 2569
PY  - 2019///
SN  - 0006-4971
SP  - 2559
TI  - The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing
T2  - Blood
UR  - http://dx.doi.org/10.1182/blood.2019000510
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000471256200004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://ashpublications.org/blood/article/133/24/2559/261461/The-heparin-binding-domain-of-von-Willebrand
UR  - http://hdl.handle.net/10044/1/83455
VL  - 133
ER  - 

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