Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction.

ABSTRACT: Sepsis is a threatening health problem and characterized by microvascular dysfunction. In this study, we verified that LPS caused the downregulation of Sirt1 and the hyperpermeability of endothelial cells. Inhibition of Sirt1 with ex527 or Sirt1 siRNA displayed a higher permeability, while activation of Sirt1 with SRT1720 reversed the LPS-induced hyperpermeability, formation of fiber stress, and disruption of VE-cadherin distribution. In pulmonary microvascular vein endothelial cells isolated from wild-type mice, Sirt1 was attenuated upon LPS, while Sirt1 was preserved in a receptor of advanced glycation end product-knockout mice. The RAGE antibody could also diminish the downregulation and ubiquitination of Sirt1 in LPS-exposed human umbilical vein endothelial cells. An LPS-induced decrea

SUBMITTER: Zhang W 

PROVIDER: S-EPMC5676476 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature