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

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.

Noncoding RNAs in Hypertension

“…112 LncRNA MRAK048635_P1 was weakly expressed in spontaneously hypertensive rats and its downregulation in VSMC stimulated the proliferation and migration of VSMCs, concomitantly with a phenotypic switch from a contractile to a secretory phenotype, key features of EHT. 113 Two lncRNAs, UCA1 and Hoxaas3, participated in the induction of proliferation of PASMCs on hypoxic stress. 114,115 Together, these preclinical studies support a role for lncRNAs in the development of hypertension and the potential for drugs targeting lncRNAs to treat hypertension.…”

Berberine ameliorates vascular dysfunction by a global modulation of lncRNA and mRNA expression profiles in hypertensive mouse aortae

“…LncRNAs, a novel class of non-coding RNAs, play critical roles at transcriptional and post-transcriptional levels in a variety of physiological and pathological processes [ 25 ]. In recent years, lncRNAs are emerged as novel modulators in the development of hypertension [ 18 , 26 , 27 ]. LncRNA TUG1 promotes the proliferation and migration of vascular smooth muscle cells (VSMCs) by affecting miR-145-5p/FGF10 axis in hypertensive state [ 28 ].…”

Noncoding RNAs in Vascular Aging

“…Accordingly, the downregulation of CASC11 in the plasma of atherosclerosis patients was found to promote VSMC proliferation and the expression of IL-9, which contributes to atherosclerosis [126]. Further, lncRNA MRAK048635 P1 exhibits low expression during hypertension and decreases its expression, promotes proliferation and migration, and inhibits apoptosis in VSMCs; this is a potentially important factor for vascular remodeling, as it affects VSMC cell function and phenotypic 9 Oxidative Medicine and Cellular Longevity switching in essential hypertension [127]. These lncRNAs are representative of many lncRNAs involved in VSMC proliferation inhibition; however, whether these lncRNAs inhibit VSMC proliferation by promoting cell cycle arrest and senescence requires further study.…”