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http://purl.uniprot.org/citations/23876886http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23876886http://www.w3.org/2000/01/rdf-schema#comment"

Background

Stent thrombosis is one of severe complications after sirolimus-eluting stent implantation. Rapamycin (sirolimus) promotes arterial thrombosis in in vivo studies. However, the underlying molecular and transcriptional mechanisms of this adverse effect have not been thoroughly investigated. This study was designed to examine the effects of rapamycin on the expression of the gene, Kruppel-like factor 2 (KLF2), and its transcriptional targets in mice.

Methods

Mice were randomly divided into four groups: the control group (intraperitoneal injection with 2.5% of dimethyl sulfoxide (DMSO) only), rapamycin group (intraperitoneal injection with 2 mg/kg of rapamycin only), Ad-LacZ + rapamycin group (carotid arterial incubation with Ad-LacZ plus intraperitoneal injection with 2 mg/kg of rapamycin 10 days later), and Ad-KLF2 + rapamycin group (carotid arterial incubation with Ad-KLF2 plus intraperitoneal injection with 2 mg/kg rapamycin 10 days later). The carotid arterial thrombosis formation was induced by FeCl3 and the time of arterial thrombosis was determined. Finally, the RNA and protein of carotid arteries were extracted for KLF2, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), endothelial nitric oxide synthase (eNOS), thrombomodulin (TM) mRNA and protein analysis.

Results

Compared with controls, treatment with rapamycin inhibited KLF2, eNOS and TM mRNA and protein expression, and enhanced TF and PAI-1 mRNA and protein expression, and shortened time to thrombotic occlusion from (1282 ± 347) seconds to (715 ± 120) seconds (P < 0.01) in vivo. Overexpression of KLF2 strongly reversed rapamycin-induced effects on KLF2, eNOS, TM, TF and PAI-1 expression. KLF2 overexpression increased the time to thrombotic occlusion to control levels in vivo.

Conclusions

Rapamycin induced an inhibition of KLF2 expression and an imbalance of anti- and pro-thrombotic gene expression, which promoted arterial thrombosis in vivo. Overexpression of KLF2 increased KLF2 expression and reversed time to thrombosis in vivo."xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/author"Xu R.X."xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/author"Zhou Y.J."xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/author"Li J.J."xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/author"Guo Y.L."xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/author"Nie X.M."xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/author"Su L.X."xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/name"Chin Med J (Engl)"xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/pages"2636-2640"xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/title"Kruppel-like factor 2 might mediate the rapamycin-induced arterial thrombosis in vivo: implications for stent thrombosis in patients."xsd:string
http://purl.uniprot.org/citations/23876886http://purl.uniprot.org/core/volume"126"xsd:string
http://purl.uniprot.org/citations/23876886http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23876886
http://purl.uniprot.org/citations/23876886http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23876886
http://purl.uniprot.org/uniprot/#_Q3V293-mappedCitation-23876886http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23876886
http://purl.uniprot.org/uniprot/#_Q60843-mappedCitation-23876886http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23876886
http://purl.uniprot.org/uniprot/#_Q9JLV7-mappedCitation-23876886http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23876886
http://purl.uniprot.org/uniprot/Q3V293http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/23876886
http://purl.uniprot.org/uniprot/Q60843http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/23876886
http://purl.uniprot.org/uniprot/Q9JLV7http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/23876886