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Smooth muscle FGF/TGF? cross talk regulates atherosclerosis progression.


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 TGF? 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/TGF? signaling cross talk was observed in vitro and in vivo In vitro, inhibition of FGF signaling increased TGF? activity, thereby promoting smooth muscle differentiation and decreasing proliferation. In vivo, smooth muscle-specific knockout of an FGF receptor adaptor Frs2? 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 TGF? activity, and increased disease severity. These results identify SMC FGF/TGF? signaling cross talk as an important regulator of SMC phenotype switch and document a major contribution of medial SMC proliferation to atherosclerotic plaque growth.

SUBMITTER: Chen PY 

PROVIDER: S-EPMC4931287 | biostudies-other | 2016 Jul

REPOSITORIES: biostudies-other

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Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression.

Chen Pei-Yu PY   Qin Lingfeng L   Li Guangxin G   Tellides George G   Simons Michael M  

EMBO molecular medicine 20160701 7


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 TGFβ 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/T  ...[more]

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