Down-regulation of lncRNA MALAT1 alleviates vascular lesion and vascular remodeling of rats with hypertension

Abstract

Objective: Recently, the effect of long non-coding RNAs (lncRNAs) in hypertension (HTN) has been identified. This study aims to explore the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HTN and its role in vascular lesion and remodeling of HTN rats. Results: LncRNA MALAT1 expression was up-regulated in HTN patients, and lncRNA MALAT1 could be an effective index of HTN diagnosis. Down-regulated MALAT1 and inhibited Notch-1 could reduce relative factor expression, including inflammation-related factors, endothelial function-related factors and oxidative stress-related factors, and inhibit apoptosis of aortic endothelial cells of HTN rats. Methods: LncRNA MALAT1 expression in HTN patients and healthy controls was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Angiotensin II (Ang II)-induced HTN rat models were injected with MALAT1-siRNA, empty lentivirus vector, Notch pathway inhibitor (DAPT) and dimethyl sulphoxide (DMSO) via caudal vein. After three-week treatment, changes of blood pressure, inflammatory factor levels, endothelial function-related factors, oxidative stress indices and apoptosis of vascular endothelial cells were determined by a series of assays. Conclusion: This study revealed that down-regulated lncRNA MALAT1 could alleviate the vascular lesion and remodeling of HTN rats, the mechanism may be related to the inhibited activation of Notch signaling pathway.

LncRNA SNHG12 alleviates hypertensive vascular endothelial injury through miR-25-3p/SIRT6 pathway

“…For example, LncRNA AK094457 was up‐regulated in hypertensive rats, and silencing AK094457 reduced arterial pressure of rats and inhibited Ang II‐induced vascular endothelial dysfunction 11 . LncRNA MALAT1 was up‐regulated in venous blood from HPT patients and vascular tissues of hypertensive rats, and silencing MALAT1 reduced vascular fibrosis and inhibited aortic EC apoptosis 12 . However, the studies focused on the regulation of LncRNAs in vascular EC injury in Ang II‐induced HPT still lack.…”

Deficiency of MicroRNA-181a Results in Transcriptome-Wide Cell Specific Changes in the Kidney that Lead to Elevated Blood Pressure and Salt Sensitivity

“…13 Examination of the top ten up- and down-regulated genes in miR-181a/b-1 KO mice showed that most genes are cell-specifically regulated (Figure 6 and Table S2). Amongst the top up-regulated genes were Stat4 in B cells (fold change=11, expression validated by real-time PCR in Figure S6) which is associated with inflammation, 14 collagen genes associated with fibrosis such as Col4a1 (fold change=1.5) in endothelial cells, Cd81 a marker of renal-resident macrophages 15 (fold change=1.2), Flt3l found in natural killer cells (only expressed in miR-181a/b-1 KO mice) which exacerbates accumulation of T cells in the kidney, 16 Malat1 found in macrophages (fold change=1.2) shown to be higher in hypertensive patients and blockade of Malat1 was able to lower BP in an animal model, 17 Notch2 in proximal tubules (only expressed in miR- 181a/b-1 KO mice) which is involved in nephron development, 18 and Polr2f found in proximal tubules (fold change=2.2) previously associated with established hypertension in a meta-analysis. 19 Several of the up-regulated genes have been previously demonstrated to have a role in renal injury, inflammation and fibrosis including Cxcl16 20 found in distal convoluted tubule cells (fold change=2.1), and Smad4 found in collecting duct principal cells (fold change=1.3).…”

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 ].…”