In:
PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 11 ( 2020-11-11), p. e0239908-
Abstract:
Increased transforming growth factor-β (TGF-β) signaling contributes to the pathophysiology of aortic aneurysm in Marfan syndrome (MFS). Recent reports indicate that a small but significant number of inflammatory cells are infiltrated into the aortic media and adventitia in MFS. However, little is known about the contribution of myeloid cells to aortic aneurysmal formation. In this study, we ablated the TGF-β type II receptor gene Tgfbr2 in myeloid cells of Fbn1 C1039G/+ MFS mice ( Fbn1 C1039G/+ ; LysM-Cre/+ ; Tgfbr2 fl/fl mice, hereinafter called Fbn1 C1039G/+ ; Tgfbr2 MyeKO ) and evaluated macrophage infiltration and TGF-β signaling in the aorta. Aneurysmal formation with fragmentation and disarray of medial elastic fibers observed in MFS mice was significantly ameliorated in Fbn1 C1039G/+ ; Tgfbr2 MyeKO mice. In the aorta of Fbn1 C1039G/+ ; Tgfbr2 MyeKO mice, both canonical and noncanonical TGF-β signals were attenuated and the number of infiltrated F4/80-positive macrophages was significantly reduced. In vitro , TGF-β enhanced the migration capacity of RAW264.7 macrophages. These findings suggest that TGF-β signaling in myeloid cells promotes aortic aneurysmal formation and its inhibition might be a novel therapeutic target in MFS.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0239908
DOI:
10.1371/journal.pone.0239908.g001
DOI:
10.1371/journal.pone.0239908.g002
DOI:
10.1371/journal.pone.0239908.g003
DOI:
10.1371/journal.pone.0239908.g004
DOI:
10.1371/journal.pone.0239908.g005
DOI:
10.1371/journal.pone.0239908.s001
DOI:
10.1371/journal.pone.0239908.s002
DOI:
10.1371/journal.pone.0239908.s003
DOI:
10.1371/journal.pone.0239908.s004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2267670-3
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