Identification of differentially‐expressed miRNAs in the subfornical organ (SFO) of the mouse brain in a slow pressor angiotensin (Ang)‐II infusion model of hypertension

Abstract

Hypertension caused by systemic Ang‐II infusion is mediated by central neurogenic mechanisms. Circulating Ang‐II interfaces with central sites lacking a blood brain barrier, e.g. SFO, which may respond to chronic Ang‐II signaling by altering gene expression. Given recent evidence suggesting that altered miRNA expression is involved in cardiovascular disease, we hypothesized that miRNA expression in the SFO is altered following slow‐pressor Ang‐II infusion. Mice were implanted subcutaneously with osmominipumps for systemic delivery of saline or Ang‐II (600ng*kg‐1*min‐1) for 2wks. Microarray analyses for miRNA expression performed on RNA from SFO punches (5 mice/sample, n=3) from Ang‐II or saline‐infused mice revealed that 5 miRNAs were differentially expressed (p <0.05). MiRNAs mmu‐miR‐133b, mmu‐miR‐24‐2* and mmu‐mir‐499 were down‐regulated, whereas, mmu‐miR‐712 and mmu‐miR‐193b were up‐regulated Sequence analysis revealed interactions of these miRNAs with many candidate genes involved in neuronal activation. For example, mmu‐miR‐712 interacts with CaMKIIa, glutathione peroxidase 3, and neural growth regulator 1, whereas mmu‐miR‐133b interacts with AP1 family members Tcfap2a and Tcfap2d. Our findings suggest that differential expression of miRNAs following Ang‐II infusion may contribute to changes in gene expression in the SFO that could lead to the development of hypertension.