Matches in SemOpenAlex for { <https://semopenalex.org/work/W2137898703> ?p ?o ?g. }
- W2137898703 endingPage "5174" @default.
- W2137898703 startingPage "5159" @default.
- W2137898703 abstract "Angioplasty and stenting is the primary treatment for flow-limiting atherosclerosis; however, this strategy is limited by pathological vascular remodeling. Using a systems approach, we identified a role for the network hub gene glutathione peroxidase-1 (GPX1) in pathological remodeling following human blood vessel stenting. Constitutive deletion of Gpx1 in atherosclerotic mice recapitulated this phenotype of increased vascular smooth muscle cell (VSMC) proliferation and plaque formation. In an independent patient cohort, gene variant pair analysis identified an interaction of GPX1 with the orphan protooncogene receptor tyrosine kinase ROS1. A meta-analysis of the only genome-wide association studies of human neointima-induced in-stent stenosis confirmed the association of the ROS1 variant with pathological remodeling. Decreased GPX1 expression in atherosclerotic mice led to reductive stress via a time-dependent increase in glutathione, corresponding to phosphorylation of the ROS1 kinase activation site Y2274. Loss of GPX1 function was associated with both oxidative and reductive stress, the latter driving ROS1 activity via s-glutathiolation of critical residues of the ROS1 tyrosine phosphatase SHP-2. ROS1 inhibition with crizotinib and deglutathiolation of SHP-2 abolished GPX1-mediated increases in VSMC proliferation while leaving endothelialization intact. Our results indicate that GPX1-dependent alterations in oxido-reductive stress promote ROS1 activation and mediate vascular remodeling." @default.
- W2137898703 created "2016-06-24" @default.
- W2137898703 creator A5000195279 @default.
- W2137898703 creator A5016363572 @default.
- W2137898703 creator A5028242375 @default.
- W2137898703 creator A5036587108 @default.
- W2137898703 creator A5038113693 @default.
- W2137898703 creator A5038904980 @default.
- W2137898703 creator A5039426271 @default.
- W2137898703 creator A5040647937 @default.
- W2137898703 creator A5041084808 @default.
- W2137898703 creator A5042828451 @default.
- W2137898703 creator A5043726462 @default.
- W2137898703 creator A5045551385 @default.
- W2137898703 creator A5046279796 @default.
- W2137898703 creator A5047494990 @default.
- W2137898703 creator A5051232840 @default.
- W2137898703 creator A5053338938 @default.
- W2137898703 creator A5055481715 @default.
- W2137898703 creator A5059696733 @default.
- W2137898703 creator A5060531836 @default.
- W2137898703 creator A5066358077 @default.
- W2137898703 creator A5067917635 @default.
- W2137898703 creator A5069201202 @default.
- W2137898703 creator A5075711252 @default.
- W2137898703 creator A5078488864 @default.
- W2137898703 creator A5084589096 @default.
- W2137898703 date "2014-11-17" @default.
- W2137898703 modified "2023-10-13" @default.
- W2137898703 title "Oxido-reductive regulation of vascular remodeling by receptor tyrosine kinase ROS1" @default.
- W2137898703 cites W11211781 @default.
- W2137898703 cites W113714250 @default.
- W2137898703 cites W13897408 @default.
- W2137898703 cites W146325010 @default.
- W2137898703 cites W1527614413 @default.
- W2137898703 cites W1594510878 @default.
- W2137898703 cites W1966078827 @default.
- W2137898703 cites W1967866270 @default.
- W2137898703 cites W1968517325 @default.
- W2137898703 cites W1969459077 @default.
- W2137898703 cites W1970203053 @default.
- W2137898703 cites W1975623017 @default.
- W2137898703 cites W1984124570 @default.
- W2137898703 cites W1988702757 @default.
- W2137898703 cites W1993222177 @default.
- W2137898703 cites W1993888853 @default.
- W2137898703 cites W1998938457 @default.
- W2137898703 cites W2000949542 @default.
- W2137898703 cites W2003291578 @default.
- W2137898703 cites W2003449292 @default.
- W2137898703 cites W2014973010 @default.
- W2137898703 cites W2016021756 @default.
- W2137898703 cites W2022319775 @default.
- W2137898703 cites W2036056488 @default.
- W2137898703 cites W2040923416 @default.
- W2137898703 cites W2040986717 @default.
- W2137898703 cites W2053954823 @default.
- W2137898703 cites W2062110035 @default.
- W2137898703 cites W2064060866 @default.
- W2137898703 cites W2074919956 @default.
- W2137898703 cites W2086944122 @default.
- W2137898703 cites W2088790008 @default.
- W2137898703 cites W2089394474 @default.
- W2137898703 cites W2101078720 @default.
- W2137898703 cites W2104128564 @default.
- W2137898703 cites W2105180954 @default.
- W2137898703 cites W2107390778 @default.
- W2137898703 cites W2119470649 @default.
- W2137898703 cites W2127639733 @default.
- W2137898703 cites W2133520037 @default.
- W2137898703 cites W2133833958 @default.
- W2137898703 cites W2133990480 @default.
- W2137898703 cites W2134724797 @default.
- W2137898703 cites W2139527140 @default.
- W2137898703 cites W2154283765 @default.
- W2137898703 cites W2154736130 @default.
- W2137898703 cites W2159675211 @default.
- W2137898703 cites W2164683872 @default.
- W2137898703 cites W2164957003 @default.
- W2137898703 cites W2168691181 @default.
- W2137898703 cites W2171342019 @default.
- W2137898703 cites W2171935912 @default.
- W2137898703 doi "https://doi.org/10.1172/jci77484" @default.
- W2137898703 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4348976" @default.
- W2137898703 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25401476" @default.
- W2137898703 hasPublicationYear "2014" @default.
- W2137898703 type Work @default.
- W2137898703 sameAs 2137898703 @default.
- W2137898703 citedByCount "38" @default.
- W2137898703 countsByYear W21378987032014 @default.
- W2137898703 countsByYear W21378987032015 @default.
- W2137898703 countsByYear W21378987032016 @default.
- W2137898703 countsByYear W21378987032017 @default.
- W2137898703 countsByYear W21378987032018 @default.
- W2137898703 countsByYear W21378987032019 @default.
- W2137898703 countsByYear W21378987032020 @default.
- W2137898703 countsByYear W21378987032021 @default.
- W2137898703 countsByYear W21378987032022 @default.