Abstract 13299: Cross Talk Between Hyper Permeability and Autophagy in Endothelial Cells With Persistent Inflammation
Introduction: Lipopolysaccharide (LPS) is known to induce endothelial dysfunction causing an increase in permeability and damage intra cellular signaling as well as known to induce autophagy. However, few studies have suggested that autophagy might interrupt cell-cell interaction through adherens junction protein, which leads to endothelial barrier dysfunction. Here we demonstrated that LPS induces autophagy, and hyper permeability of lung endothelial cells and this can be prevented by the combinatorial treatment with 5-Aza 2 deoxycytidine and Tubastatin A (HDAC6 inhibitor) (referred as Aza+TBSA).
Hypothesis: We hypothesize that treatment with the combination of Aza+TBSA inhibits autophagy and restores vascular integrity after LPS induced vascular hyper permeability.
Methods and Results: In this study, we have used LPS to induce hyper permeability and autophagy and mTOR inhibitor Rapamycin used as a positive control for autophagy in mouse lung endothelial cells (MLECs). Our Western analysis data showed that LPS and Rapamycin induce autophagy, which is indicated by the increased level of known autophagy markers LC3 and beclin-1, and decreased VE-cadherin expression in MLECs induced with LPS or Rapamycin. Where as treatment with Aza+TBSA significantly reduced the effect of LPS induced autophagy markers and increased VE-cadherin expression (Fig. 1A). Our immunofluorescence analysis also showed a decreased expression of LC3 when the LPS induced MLECs was treated with Aza+TBSA (Fig. 1B).
Conclusions: These data suggest that Aza+TBSA treatment can rescue endothelial barrier dysfunction and prevent autophagy in LPS-induced MLECs, indicating that LPS-induced vascular leakage is dependent on autophagy. These results support a therapeutic potential of Aza+TBSA combination for patients with acute lung injury.
Author Disclosures: S. Samanta: None. S. Rajasingh: None. L. Chen: None. T. Cao: None. N. Drosos: None. B. Dawn: None. J. Rajasingh: None.
- © 2016 by American Heart Association, Inc.