Abstract W P406: Regulation Of MicroRNAs By Angiotensin II In Neurovascular Niche
In adult brain, neuronal stem cells (NSC) are located in the neurovascular niche therefore, vascular cells play an important role in creating a healthy environment for adult neurogenesis. Several laboratories including ours have demonstrated that Angiotensin II (AngII)-induced hypertension affects numerous vascular functions by causing oxidative stress, vascular inflammation and endothelial dysfunction. Further, the available evidence suggests that blood-brain barrier (BBB) deregulation is an indirect consequence of cerebrovascular inflammation. Of these, AngII effect on BBB dysfunction has been reported, and is implicated in the pathogenesis of stroke, small vessel disease, vascular dementia and Alzheimer’s disease. In this regard, miRNAs emerged as key players in the development of vascular and neurodegenerative diseases. In here, we studied the effects of AngII on adult NSC and brain endothelial cell (BEC) miRNAs regulation and their interaction focusing on a specific miRNAs that were selected due to their role in other vascular systems. We used primary mouse NSC and BEC culture model to study the effects of AngII on miR-15, -34a, -155 and -let7 expression using qPCR. AngII 100nm induced expression of miR-15 in both neurospheres and BEC by 2 and 2.5-fold respectively after one hr. miR-34a expression was induced by 3.5-fold in neurospheres and by 3-fold in BEC in 24-hr. Mir-155 expression was elevated in neurospheres by 2-fold and in BEC by 3-fold after 45-min. miR-let7 was increased in neurospheres and BEC by 4-fold in 15 min, and remained induced in EC for one hr. These miRNAs expression changes were accompanied by increased protein expression of C/EBPβ, pCREB, and p38MAPK. However, Ets1 expression was downregulated in both neurospheres and BEC. These results indicate that AngII has major effects on NSC and BEC through deregulating miRNAs and protein levels involved in this phenomenon. Further studies are needed to explore the mechanisms involved.
Author Disclosures: T. Chabrashvili: None. B. Sawaya: None.
- © 2015 by American Heart Association, Inc.