Profiles of long noncoding RNAs in hypertensive rats: long noncoding RNA XR007793 regulates cyclic strain-induced proliferation and migration of vascular smooth muscle cells

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Abstract

Background:

Long noncoding RNAs (lncRNAs) are being discovered in multiple diseases at a rapid pace. However, the contribution of lncRNAs to hypertension remains largely unknown. In hypertension, the vascular walls are exposed to abnormal mechanical cyclic strain, which leads to vascular remodelling. Here, we investigated the mechanobiological role of lncRNAs in hypertension.

Methods and results:

Differences in the lncRNAs and mRNAs between spontaneously hypertensive rats and Wistar–Kyoto rats were screened using a gene microarray. The results showed that 68 lncRNAs and 255 mRNAs were upregulated in the aorta of spontaneously hypertensive rats, whereas 167 lncRNAs and 272 mRNAs were downregulated. Expressions of the screened lncRNAs, including XR007793, were validated by real-time PCR. A coexpression network was composed, and gene function was analysed using Ingenuity Pathway Analysis. In vitro, vascular smooth muscle cells (VSMCs) were subjected to cyclic strain at a magnitude of 5 (physiological normotensive cyclic strain) or 15% (pathological hypertensive cyclic strain) by Flexcell-4000T. A total of 15% cyclic strain increased XR007793 expression. XR007793 knockdown attenuated VSMC proliferation and migration and inhibited coexpressed genes such as signal transducers and activators of transcription 2 (stat2), LIM domain only 2 (lmo2) and interferon regulatory factor 7 (irf7).

Conclusion:

The profile of lncRNAs was varied in response to hypertension, and pathological elevated cyclic strain may play crucial roles during this process. Our data revealed a novel mechanoresponsive lncRNA-XR007793, which modulates VSMC proliferation and migration, and participates in vascular remodelling during hypertension.

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