Downregulation of DLGAP1-Antisense RNA 1 Alleviates Vascular Endothelial Cell Injury Via Activation of the Phosphoinositide 3-kinase/Akt Pathway Results from an Acute Limb Ischemia Rat Model.

Objective: This study aimed to investigate the effect of long non-coding RNA (lncRNA) DLGAP1 antisense RNA 1 (DLGAP1-AS1) on vascular endothelial cell (VEC) injury via the phosphoinositide 3-kinase (PI3K)/Akt pathway in rat models of acute lower limb ischaemia-reperfusion (I/R).
Methods: Differentially expressed lncRNAs related to I/R were screened using the gene expression omnibus database. Acute lower limb I/R models were induced in male Wistar rats, in which the regulatory mechanisms of DLGAP1-AS1 silencing were analysed after the treatment of small interfering RNA (siRNA) against DLGAP1-AS1 or an inhibitor of the PI3K/Akt pathway. The relationship between DLGAP1-AS1 and the PI3K/Akt pathway was analysed. The levels of tumour necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1), as well as malondialdehyde (MDA) concentration and creatine kinase (CK) activity, were measured. The number of circulating endothelial cells (CECs) and apoptosis of VECs were identified.
Results: Microarray based analysis indicated that DLGAP1-AS1 was highly expressed in I/R, which was further confirmed by detection of expression in rat models of acute lower limb I/R. Notably, the treatment of siRNA against DLGAP1-AS1 led to the activation of the PI3K/Akt pathway. In response to siRNA against DLGAP1-AS1, the levels of TNF-α and VCAM-1 were decreased, and MDA concentration and CK activity was downregulated. Reduced CEC numbers and suppressed VEC apoptosis were also observed.
Conclusion: DLGAP1-AS1 silencing could further suppress the oxidative stress, exert an anti-apoptosis effect, and reduce inflammatory reaction, whereby VEC injury is alleviated by activation of the PI3K/Akt pathway in rats with acute lower limb I/R.
(Copyright © 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)