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- W2127697798 abstract "Vascular fibrosis is a major complication of hypertension and atherosclerosis, yet it is largely untreatable. Natriuretic peptides (NPs) repress fibrogenic activation of vascular smooth muscle cells (VSMCs), but the intracellular mechanism mediating this effect remains undetermined. Here we show that inhibition of RhoA through phosphorylation at Ser188, the site targeted by the NP effector cyclic GMP (cGMP)-dependent protein kinase I (cGK I), is critical to fully exert antifibrotic potential. cGK I(+/-) mouse blood vessels exhibited an attenuated P-RhoA level and concurrently increased RhoA/ROCK signaling. Importantly, cGK I insufficiency caused dynamic recruitment of ROCK into the fibrogenic programs, thereby eliciting exaggerated vascular hypertrophy and fibrosis. Transgenic expression of cGK I-unphosphorylatable RhoA(A188) in VSMCs augmented ROCK activity, vascular hypertrophy, and fibrosis more prominently than did that of wild-type RhoA, consistent with the notion that RhoA(A188) escapes the intrinsic inhibition by cGK I. Additionally, VSMCs expressing RhoA(A188) became refractory to the antifibrotic effects of NPs. Our results identify cGK I-mediated Ser188 phosphorylation of RhoA as a converging node for pro- and antifibrotic signals and may explain how diminished cGMP signaling, commonly associated with vascular malfunction, predisposes individuals to vascular fibrosis." @default.
- W2127697798 created "2016-06-24" @default.
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- W2127697798 date "2009-11-01" @default.
- W2127697798 modified "2023-09-27" @default.
- W2127697798 title "Cyclic GMP Kinase and RhoA Ser188 Phosphorylation Integrate Pro- and Antifibrotic Signals in Blood Vessels" @default.
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- W2127697798 cites W1902300865 @default.
- W2127697798 cites W1925229827 @default.
- W2127697798 cites W1966222469 @default.
- W2127697798 cites W1976440445 @default.
- W2127697798 cites W1979344355 @default.
- W2127697798 cites W1981269419 @default.
- W2127697798 cites W1986718308 @default.
- W2127697798 cites W1988454624 @default.
- W2127697798 cites W1988824186 @default.
- W2127697798 cites W1989815448 @default.
- W2127697798 cites W1994807255 @default.
- W2127697798 cites W1994965373 @default.
- W2127697798 cites W2003431971 @default.
- W2127697798 cites W2014575233 @default.
- W2127697798 cites W2016193552 @default.
- W2127697798 cites W2017557087 @default.
- W2127697798 cites W2019731805 @default.
- W2127697798 cites W2019822857 @default.
- W2127697798 cites W2035348154 @default.
- W2127697798 cites W2035620169 @default.
- W2127697798 cites W2040663949 @default.
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- W2127697798 cites W2053257956 @default.
- W2127697798 cites W2060072724 @default.
- W2127697798 cites W2063679739 @default.
- W2127697798 cites W2075225305 @default.
- W2127697798 cites W2076597032 @default.
- W2127697798 cites W2077342384 @default.
- W2127697798 cites W2080032926 @default.
- W2127697798 cites W2080814134 @default.
- W2127697798 cites W2080909963 @default.
- W2127697798 cites W2084660313 @default.
- W2127697798 cites W2092585489 @default.
- W2127697798 cites W2099309899 @default.
- W2127697798 cites W2101072720 @default.
- W2127697798 cites W2103839593 @default.
- W2127697798 cites W2107704180 @default.
- W2127697798 cites W2109679295 @default.
- W2127697798 cites W2117968545 @default.
- W2127697798 cites W2118103351 @default.
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- W2127697798 cites W2128725121 @default.
- W2127697798 cites W2131036882 @default.
- W2127697798 cites W2132106701 @default.
- W2127697798 cites W2133570574 @default.
- W2127697798 cites W2137377367 @default.
- W2127697798 cites W2138742704 @default.
- W2127697798 cites W2147758809 @default.
- W2127697798 cites W2148262525 @default.
- W2127697798 cites W2149196587 @default.
- W2127697798 cites W2150621532 @default.
- W2127697798 cites W2154449412 @default.
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- W2127697798 cites W2166409314 @default.
- W2127697798 cites W2167414705 @default.
- W2127697798 cites W2169804106 @default.
- W2127697798 cites W2170497762 @default.
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- W2127697798 doi "https://doi.org/10.1128/mcb.00225-09" @default.
- W2127697798 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2772562" @default.
- W2127697798 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19737918" @default.
- W2127697798 hasPublicationYear "2009" @default.
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