摘要：

Protein Tyrosine Phosphatase 1B (PTP1B) modulates endoplasmic reticulum stress (ERS). However, whether PTP1B regulates ERS-nduced endothelial dysfunction is unknown. To test the hypothesis that PTP1B deletion protects against ERS-mediated endothelial dysfunction, ERS was induced with either tunicamycin (TUNICA) in aortic rings from PTP1B null (KO) and control mice (WT) or by treating WT and KO mice with STZ for 4 weeks. Assessment of the vascular function demonstrated that TUNICA reduced endothelial function by 30% in WT mice while endothelial function remained intact in KO mice. ACh relaxation was completely abolished by LNAME but neither tempol nor indomethacin improved ERS-mediated endothelial dysfunction, suggesting that neither ROS nor COX derivatives are involved in the dysfunction. TUNICA blunted Ca2+-mediated relaxation in WT mice only, suggesting that PTP1B deletion preserves eNOS sensitivity to Ca2+. Four weeks of STZ treatment significantly reduced endothelial function in WT mice. Acute treatment of aortic rings with the ERS inhibitor TUDCA restored endothelial function and confirmed that type I diabetes induces endothelial dysfunction via ERS. Despite a higher glycemia compared to WT mice, PTP1B KO mice did not develop an endothetlial dysfunction in response to STZ and TUDCA did not affect vascular relaxation. Consequently, PTP1B appears to be a key target to prevent endothelial function.

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