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Endothelial thioredoxin interacting protein (TXNIP) modulates endothelium-dependent vasorelaxation in hyperglycemia.
Lam, Yuen Ting; Tan, Richard P; Michael, Praveesuda; Yang, Nianji; Dunn, Louise L; Cooke, John P; Celermajer, David S; Wise, Steven G; Ng, Martin K C.
Afiliação
  • Lam YT; School of Medical Sciences, Chronic Disease Theme, University of Sydney, Sydney 2006, Australia; Charles Perkins Centre, University of Sydney, Australia.
  • Tan RP; School of Medical Sciences, Chronic Disease Theme, University of Sydney, Sydney 2006, Australia; Charles Perkins Centre, University of Sydney, Australia; Sydney Nano, The University of Sydney, Sydney, Australia.
  • Michael P; School of Medical Sciences, Chronic Disease Theme, University of Sydney, Sydney 2006, Australia; Charles Perkins Centre, University of Sydney, Australia.
  • Yang N; School of Medical Sciences, Chronic Disease Theme, University of Sydney, Sydney 2006, Australia; Charles Perkins Centre, University of Sydney, Australia; Sydney Nano, The University of Sydney, Sydney, Australia.
  • Dunn LL; Heart Research Institute, Sydney, Australia.
  • Cooke JP; Center for Cardiovascular Regeneration, Department of Cardiovascular Science, Houston Methodist Research Institute, Houston, USA.
  • Celermajer DS; Heart Research Institute, Sydney, Australia; Sydney Medical School, Central Clinical School, University of Sydney, Sydney 2006, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney 2050, Australia.
  • Wise SG; School of Medical Sciences, Chronic Disease Theme, University of Sydney, Sydney 2006, Australia; Charles Perkins Centre, University of Sydney, Australia; Sydney Nano, The University of Sydney, Sydney, Australia.
  • Ng MKC; Sydney Medical School, Central Clinical School, University of Sydney, Sydney 2006, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney 2050, Australia. Electronic address: martin.ng@sydney.edu.au.
Microvasc Res ; 143: 104396, 2022 09.
Article em En | MEDLINE | ID: mdl-35644243
ABSTRACT
Endothelial dysfunction, hallmarked by an imbalance between vasoconstriction and vasorelaxation, is associated with diabetes. Thioredoxin Interacting protein (TXNIP), controlled by an exquisitely glucose sensitive gene, is increasingly recognized for its role in diabetes. However, the role of TXNIP in modulating diabetes-related endothelial dysfunction remains unclear. To elucidate the role of TXNIP, we generated two novel mouse strains; endothelial-specific TXNIP knockout (EKO) and a Tet-O inducible, endothelial-specific TXNIP overexpression (EKI). Hyperglycemia was induced by streptozotocin (STZ) treatment in floxed control (fl/fl) and EKO mice. Doxycycline (DOX) was given to EKI mice to induce endothelial TXNIP overexpression. The ablation of endothelial TXNIP improved glucose tolerance in EKO mice. Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in STZ-treated fl/fl mice while this STZ impaired vasorelaxation was attenuated in EKO mice. Hyperglycemia induction of NLRP3 and reductions in Akt and eNOS phosphorylation were also mitigated in EKO mice. Overexpression of endothelial TXNIP did not impair glucose tolerance in DOX-treated EKI mice, however induction of endothelial TXNIP led to impaired vasorelaxation in EKI mice. This was associated with increased NLRP3 and reduced Akt and eNOS activation. In conclusion, deletion of endothelial TXNIP is protective against and overexpression of endothelial TXNIP induces endothelial dysfunction; thus, endothelial TXNIP plays a critical role in modulating endothelial dysfunction.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tiorredoxinas / Vasodilatação / Endotélio / Hiperglicemia Limite: Animals Idioma: En Revista: Microvasc Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tiorredoxinas / Vasodilatação / Endotélio / Hiperglicemia Limite: Animals Idioma: En Revista: Microvasc Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Austrália