Background: Cerebral ischemia/reperfusion (I/R) injury leads to cerebrovascular dysfunction characterized by endothelial cell injury or death. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has been reported to be associated with endothelial dysfunction. Our study aimed to investigate the effect of MALAT1 on vascular endothelium.
Methods: In this study, oxygen-glucose deprivation and reoxygenation (OGD-R) were used as in vitro studies to investigate the role of MALAT1 in I/R-induced apoptosis of cerebrovascular endothelial cells in an I/R injury model. Primary human brain microvascular endothelial cells were cultured on the condition of OGD-R and MALAT1 expression levels and apoptosis were measured at 6, 9, 12, 24 and 36 h after reoxygenation. The expression of MALAT1 and the apoptosis rate of cells exposed to OGD-R showed the trend of reoxygenation. The kit detected the expression of ROS and PI3K, and the change of Akt signal was detected by Western-blot.
Results: After OGD-R, over-expression of MALAT1 lentivirus increased phosphatidylinositol 3-kinase (PI3K) activity and activation of Akt phosphorylation, while decreased apoptosis and caspase 3 activity. Moreover, these effects could be successfully eliminated by treating with a PI3K inhibitor (wortmannin). In contrast, knockdown of MALAT1 lentivirus reduced PI3K activity and Akt phosphorylation, while increased apoptosis and caspase 3 activity. Overexpression or knockdown of MALAT1 had no significant effect on that OGD-R-induced reactive oxygen species (ROS) production.
Conclusions: This study first proposed that lncRNA MALAT1 can protect human cerebrovascular endothelial cells from OGD-R-induced apoptosis through a PI3K-dependent mechanism. These findings suggest that MALAT1 may be a potential new therapeutic target for brain I/R injury.
Keywords: MALAT1; apoptosis; endothelial cells; oxygen–glucose deprivation; reoxygenation.