LncRNA MRAK048635_P1 is critical for vascular smooth muscle cell function and phenotypic switching in essential hypertension.

Genqiang Fang,Liya Huang,Xianxian Zhao,Jia Qi

doi:10.1042/bsr20182229

Abstract

Vascular remodeling caused by essential hypertension is a leading cause of death in patients, and vascular smooth muscle cell (VSMC) dysfunction and phenotypic switching result in vascular remodeling. Therefore, inhibiting cell dysfunction and phenotypic switching in VSMCs may be a new treatment strategy for essential hypertension. The aim of the current study is to explore the roles of long non-coding RNA (lncRNA) MRAK048635_P1 in VSMC function and phenotypic switching. The MRAK048635_P1 level was determined in spontaneously hypertensive rats (SHRs) and VSMCs isolated from SHRs. MRAK048635_P1 was knocked down using a specific siRNA in VSMCs isolated from the thoracic aorta of SHRs and Wistar–Kyoto rats. Then, the proliferation and migration of VSMCs were determined using a cell counting kit-8 (CCK-8), a 3H labeling method, a transwell assay, and a wound healing assay. Flow cytometry was used to test the effect of MRAK048635_P1 on VSMC apoptosis. The protein and mRNA levels of associated genes were measured through Western blotting, immunofluorescence, and Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). MRAK048635_P1 showed low expression during hypertension in vivo and in vitro. Down-regulation of lncRNA MRAK048635_P1 promoted proliferation and migration and inhibited apoptosis in VSMCs isolated from healthy rat vascular tissue and SHR-derived VSMCs. Importantly, we also found that down-regulation of MRAK048635_P1 could induce VSMC phenotypic switching from a contractile to a secretory phenotype. In conclusion, our findings reveal that decreased MRAK048635_P1 is probably an important factor for vascular remodeling by affecting VSMC cell function and phenotypic switching in essential hypertension.

Highlights

Essential hypertension is a clinical syndrome characterized by increased systemic arterial blood pressure, accompanied by functional or organic damage to the heart, brain, kidney, and other organs [1]
To explore the biological role of Long non-coding RNA (lncRNA) in vascular smooth muscle cell (VSMC) in hypertension, Yao et al [13] screened lncRNA expression profiles in the aortas of spontaneously hypertensive rats (SHRs) and Wistar–Kyoto rats (WKYs) using a gene microarray, and the results showed that 68 lncRNAs were up-regulated and 167 lncRNAs were down-regulated in the SHR aorta
Low nuclear expression of MRAK048635 P1 was observed in both SHR and WKY samples, but the expression of MRAK048635 P1 was lower in cytoplasm in SHR samples compared with WKY samples (Figure 1C)

Summary

Introduction

Essential hypertension is a clinical syndrome characterized by increased systemic arterial blood pressure (systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg), accompanied by functional or organic damage to the heart, brain, kidney, and other organs [1]. A continuous increase in blood pressure leads to vascular remodeling and vascular dysfunction, which is the leading cause of death in patients [2,3]. Previous studies have shown that abnormal proliferation, migration, invasion, and phenotypic switching of vascular smooth muscle (VSM) cells (VSMCs) are important causes of vascular remodeling [4,5]. Inhibiting cell dysfunction and phenotypic switching in VSMCs may represent a new treatment strategy for essential hypertension. Long non-coding RNA (lncRNA) greater than 200 nts in length is a class of important non-coding transcripts [6]. LncRNAs can regulate the expression of target genes at the transcriptional and License 4.0 (CC BY)

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