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Publication
Smooth muscle FGF/TGFß cross talk regulates atherosclerosis progression.
Authors Chen PY, Qin L, Li G, Tellides G, Simons M
Submitted By Submitted Externally on 7/25/2018
Status Published
Journal EMBO molecular medicine
Year 2016
Date Published 7/1/2016
Volume : Pages 8 : 712 - 28
PubMed Reference 27189169
Abstract The conversion of vascular smooth muscle cells (SMCs) from contractile to
proliferative phenotype is thought to play an important role in atherosclerosis.
However, the contribution of this process to plaque growth has never been fully
defined. In this study, we show that activation of SMC TGFß signaling, achieved
by suppression of SMC fibroblast growth factor (FGF) signaling input, induces
their conversion to a contractile phenotype and dramatically reduces
atherosclerotic plaque size. The FGF/TGFß signaling cross talk was observed
in vitro and in vivo In vitro, inhibition of FGF signaling increased TGFß
activity, thereby promoting smooth muscle differentiation and decreasing
proliferation. In vivo, smooth muscle-specific knockout of an FGF receptor
adaptor Frs2a led to a profound inhibition of atherosclerotic plaque growth when
these animals were crossed on Apoe(-/-) background and subjected to a high-fat
diet. In particular, there was a significant reduction in plaque cellularity,
increase in fibrous cap area, and decrease in necrotic core size. In agreement
with these findings, examination of human coronary arteries with various degrees
of atherosclerosis revealed a strong correlation between the activation of FGF
signaling, loss of TGFß activity, and increased disease severity. These results
identify SMC FGF/TGFß signaling cross talk as an important regulator of SMC
phenotype switch and document a major contribution of medial SMC proliferation
to atherosclerotic plaque growth.




Strains




Genes
SymbolDescription
Apoeapolipoprotein E
Frs2fibroblast growth factor receptor substrate 2

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