Dynamic rewiring of microRNA networks in the brainstem autonomic control circuits during hypertension development in the female spontaneously hypertensive rat.

Abstract

We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine miRNAs in pathways related to neuronal plasticity and autonomic regulation to construct a putative miRNA-target gene network involved in the development of neurogenic hypertension. We analyzed the dynamic correlations between the miRNAs and their putative targets to identify the regulatory interactions shifting between WKY and SHR. Comparing the results with previously published data in male SHR and WKY identified miRNA network dynamics specific to female SHR during hypertension development. Collectively, our results point to distinct rewiring of the miRNA regulatory networks governing angiotensin signaling and homeostasis, neuronal plasticity, and inflammatory processes contributing to the development of hypertension in female SHR.NEW & NOTEWORTHY Hypertension is the primary risk factor for cardiovascular complications and stroke. The microRNA expression changes in the central nervous system circuits driving hypertension development are understudied. Here, we show that microRNA-mediated regulatory networks are dynamically rewired during the development of high blood pressure phenotype by targeting key signaling pathways, neuronal plasticity, and inflammatory processes in a female rat model of human essential hypertension.