Long non-coding RNA MALAT1 promotes cardiac remodeling in hypertensive rats by inhibiting the transcription of MyoD

Abstract

Hypertension is the leading preventable cause of premature deaths worldwide. Although long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) has been identified to play important roles in the development of cardiovascular diseases, the regulatory function of lncRNA MALAT1 in hypertension remains poorly understood. This study aimed to explore the role of lncRNA MALAT1 in spontaneously hypertensive rats (SHRs). LncRNA MALAT1 was determined to be elevated and MyoD to be reduced in myocardial tissues and thoracic aortic vascular tissues of SHRs. Over-expression of lncRNA MALAT1 caused severe myocardial fibrosis in SHRs. In addition, lncRNA MALAT1 over-expression in vitro enhanced arterial smooth muscle cells (ASMCs) activity and fibrosis of SHRs, which, was rescued by over-expressed MyoD. Furthermore, lncRNA MALAT1 transcripts were found to be highly enriched in the nucleus, and lncRNA MALAT1 suppressed the transactivation of MyoD. Moreover, lncRNA MALAT1 was found to recruit Suv39h1 to MyoD-binding loci, leading to H3K9me3 trimethylation and down-regulation of the target gene. Taken conjointly, this study revealed an important role of lncRNA MALAT1 in promoting cardiac remodeling in hypertensive rats by inhibiting the transcription of MyoD. These results highlight the value of lncRNA MALAT1 as a therapeutic target for the management of hypertension.

MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension

“…However, the results are not optimistic due to the complicated pathology of hypertension [34]. Vascular remodeling is a process of vascular structural changes that involves several cellular processes, including cell proliferation, migration, inflammation, and apoptosis [26, 35]. Physiological remodeling occurs as an adaptive response to hemodynamic and age-related changes [36, 37].…”

“…First, 150 mg/kg pentobarbital sodium was intraperitoneally injected into 5 SHRs to euthanize the SHRs on an aseptic operating table as described previously [26]. Subsequently, the cardiopulmonary tissues were rapidly resected and preserved in aseptic Hanks solution containing penicillin-streptomycin (15140-122, Gibco, Waltham, MA, USA).…”

“…Subsequently, the cardiopulmonary tissues were rapidly resected and preserved in aseptic Hanks solution containing penicillin-streptomycin (15140-122, Gibco, Waltham, MA, USA). Finally, ASMCs were swiftly separated from the thoracic artery tissues under an operating microscope as described before [26]. ASMCs were cultured in a culture flask.…”

Long Non-Coding RNAs (lncRNAs) in Cardiovascular Disease Complication of Type 2 Diabetes

“…Inhibition of MALAT1 expression rescued the rats’ cardiac function due to a restoration of the PI3K/AKT signaling pathway [ 148 ]. Studies in the rat model of hypertension showed that MALAT1 expression was increased in the heart [ 149 , 150 ]. Overexpression of MALAT1 caused severe cardiac fibrosis and remodeling by reducing the expression of MyoD that is responsible for the contractile phenotype of the heart [ 149 ].…”

“…Studies in the rat model of hypertension showed that MALAT1 expression was increased in the heart [ 149 , 150 ]. Overexpression of MALAT1 caused severe cardiac fibrosis and remodeling by reducing the expression of MyoD that is responsible for the contractile phenotype of the heart [ 149 ]. MALAT1 recruits the Suv39h1, a histone methyltransferase enzyme, to MyoD loci and causes H3K9me3 trimethylation to silence MyoD expression [ 149 ].…”