Targeting the intragraft microenvironment and the development of chronic allograft rejection.

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Version: author
Serval ID
serval:BIB_39F41380CB89
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Targeting the intragraft microenvironment and the development of chronic allograft rejection.
Journal
Human Immunology
Author(s)
Dormond O., Dufour M., Seto T., Bruneau S., Briscoe D.M.
ISSN
1879-1166 (Electronic)
ISSN-L
0198-8859
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
73
Number
12
Pages
1261-1268
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Abstract
In this review, we discuss a paradigm whereby changes in the intragraft microenvironment promote or sustain the development of chronic allograft rejection. A key feature of this model involves the microvasculature including (a) endothelial cell (EC) destruction, and (b) EC proliferation, both of which result from alloimmune leukocyte- and/or alloantibody-induced responses. These changes in the microvasculature likely create abnormal blood flow patterns and thus promote local tissue hypoxia. Another feature of the chronic rejection microenvironment involves the overexpression of vascular endothelial growth factor (VEGF). VEGF stimulates EC activation and proliferation and it has potential to sustain inflammation via direct interactions with leukocytes. In this manner, VEGF may promote ongoing tissue injury. Finally, we review how these events can be targeted therapeutically using mTOR inhibitors. EC activation and proliferation as well as VEGF-VEGFR interactions require PI-3K/Akt/mTOR intracellular signaling. Thus, agents that inhibit this signaling pathway within the graft may also target the progression of chronic rejection and thus promote long-term graft survival.
Pubmed
Web of science
Open Access
Yes
Create date
17/01/2013 18:20
Last modification date
20/08/2019 13:29
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