Fibrin networks regulate protein transport during thrombus development.

Thromboembolic disease is a leading cause of morbidity and mortality worldwide. In the last several years there have been a number of studies attempting to identify mechanisms that stop thrombus growth. This paper identifies a novel mechanism related to formation of a fibrin cap. In particular, prot...

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Autores principales:	Oleg V Kim, Zhiliang Xu, Elliot D Rosen, Mark S Alber
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/76ec3e7e41a74d47b7ff6f43b7025e27
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spelling	oai:doaj.org-article:76ec3e7e41a74d47b7ff6f43b7025e272021-11-18T05:52:05ZFibrin networks regulate protein transport during thrombus development.1553-734X1553-735810.1371/journal.pcbi.1003095https://doaj.org/article/76ec3e7e41a74d47b7ff6f43b7025e272013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23785270/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Thromboembolic disease is a leading cause of morbidity and mortality worldwide. In the last several years there have been a number of studies attempting to identify mechanisms that stop thrombus growth. This paper identifies a novel mechanism related to formation of a fibrin cap. In particular, protein transport through a fibrin network, an important component of a thrombus, was studied by integrating experiments with model simulations. The network permeability and the protein diffusivity were shown to be important factors determining the transport of proteins through the fibrin network. Our previous in vivo studies in mice have shown that stabilized non-occluding thrombi are covered by a fibrin network ('fibrin cap'). Model simulations, calibrated using experiments in microfluidic devices and accounting for the permeable structure of the fibrin cap, demonstrated that thrombin generated inside the thrombus was washed downstream through the fibrin network, thus limiting exposure of platelets on the thrombus surface to thrombin. Moreover, by restricting the approach of resting platelets in the flowing blood to the thrombus core, the fibrin cap impaired platelets from reaching regions of high thrombin concentration necessary for platelet activation and limited thrombus growth. The formation of a fibrin cap prevents small thrombi that frequently develop in the absence of major injury in the 60000 km of vessels in the body from developing into life threatening events.Oleg V KimZhiliang XuElliot D RosenMark S AlberPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 6, p e1003095 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Oleg V Kim Zhiliang Xu Elliot D Rosen Mark S Alber Fibrin networks regulate protein transport during thrombus development.
description	Thromboembolic disease is a leading cause of morbidity and mortality worldwide. In the last several years there have been a number of studies attempting to identify mechanisms that stop thrombus growth. This paper identifies a novel mechanism related to formation of a fibrin cap. In particular, protein transport through a fibrin network, an important component of a thrombus, was studied by integrating experiments with model simulations. The network permeability and the protein diffusivity were shown to be important factors determining the transport of proteins through the fibrin network. Our previous in vivo studies in mice have shown that stabilized non-occluding thrombi are covered by a fibrin network ('fibrin cap'). Model simulations, calibrated using experiments in microfluidic devices and accounting for the permeable structure of the fibrin cap, demonstrated that thrombin generated inside the thrombus was washed downstream through the fibrin network, thus limiting exposure of platelets on the thrombus surface to thrombin. Moreover, by restricting the approach of resting platelets in the flowing blood to the thrombus core, the fibrin cap impaired platelets from reaching regions of high thrombin concentration necessary for platelet activation and limited thrombus growth. The formation of a fibrin cap prevents small thrombi that frequently develop in the absence of major injury in the 60000 km of vessels in the body from developing into life threatening events.
format	article
author	Oleg V Kim Zhiliang Xu Elliot D Rosen Mark S Alber
author_facet	Oleg V Kim Zhiliang Xu Elliot D Rosen Mark S Alber
author_sort	Oleg V Kim
title	Fibrin networks regulate protein transport during thrombus development.
title_short	Fibrin networks regulate protein transport during thrombus development.
title_full	Fibrin networks regulate protein transport during thrombus development.
title_fullStr	Fibrin networks regulate protein transport during thrombus development.
title_full_unstemmed	Fibrin networks regulate protein transport during thrombus development.
title_sort	fibrin networks regulate protein transport during thrombus development.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/76ec3e7e41a74d47b7ff6f43b7025e27
work_keys_str_mv	AT olegvkim fibrinnetworksregulateproteintransportduringthrombusdevelopment AT zhiliangxu fibrinnetworksregulateproteintransportduringthrombusdevelopment AT elliotdrosen fibrinnetworksregulateproteintransportduringthrombusdevelopment AT marksalber fibrinnetworksregulateproteintransportduringthrombusdevelopment
_version_	1718424736856276992

Fibrin networks regulate protein transport during thrombus development.

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