Dataset Information

LincRNA-p21 alleviates atherosclerosis progression through regulating the miR-221/SIRT1/Pcsk9 axis.

ABSTRACT: Atherosclerosis (AS) is the main aetiology of coronary heart disease, cerebral infarction and peripheral vascular disease in humans. Long-noncoding RNA (LincRNA)-p21 has been reported to participate in the development of AS. Therefore, this study was designed to investigate the mechanism of LincRNA-p21 on suppressing the development of AS. We fed ApoE^-/- mice with a high-fat diet to induce an AS mouse model where the lesion area of AS and the extent of lipid deposition were measured. The binding of LincRNA-p21 and miR-221 or miR-221 and SIRT1 was measured using a dual luciferase reporter gene assay and RIP. Following loss- and gain- function assays, CCK8, EdU, Transwell assay and scratch test were performed to determine the biological processes of human aortic endothelial cells (HAECs). miR-221 was highly expressed while SIRT1 was poorly expressed in AS. LincRNA-p21 acted as a sponge for miR-221. miR-221 targeted and negatively regulated the expression of SIRT1. LincRNA-p21 promoted the deacetylation of Pcsk9 by SIRT1 by competitively binding to miR-221, whereby promoting HAEC proliferation, migration and tube formation. In conclusion, LincRNA-p21 acted as a molecular sponge for miR-221 to promote deacetylation of the promoter region of Pcsk9 by SIRT1, therefore preventing the development of AS.

SUBMITTER: Wang H

PROVIDER: S-EPMC8500963 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LincRNA-p21 alleviates atherosclerosis progression through regulating the miR-221/SIRT1/Pcsk9 axis.

Wang Haojie H He Fei F Liang Bing B Jing Yuanhu Y Zhang Pei P Liu Weichao W Zhu Bowen B Dou Dongmei D

Journal of cellular and molecular medicine 20210919 19

Atherosclerosis (AS) is the main aetiology of coronary heart disease, cerebral infarction and peripheral vascular disease in humans. Long-noncoding RNA (LincRNA)-p21 has been reported to participate in the development of AS. Therefore, this study was designed to investigate the mechanism of LincRNA-p21 on suppressing the development of AS. We fed ApoE<sup>-/-</sup> mice with a high-fat diet to induce an AS mouse model where the lesion area of AS and the extent of lipid deposition were measured. ...[more]

PMID: 34541816

Similar Datasets

Project description:BackgroundOur prior studies have shown that inflammation may play an important triggering role during the process of denervated muscle atrophy. The nonsteroidal anti-inflammatory drug aspirin exhibits the effect of anti-inflammatory factors. This study will investigate the protective effect of aspirin on denervated muscle atrophy and the underlying mechanism.MethodsMouse models of denervated muscle atrophy were established. The protective effect of aspirin (20 mg/kg/d, i.p.) on denervated muscle atrophy was analyzed using the wet weight ratio of tibialis anterior (TA) muscle and muscle fiber cross-sectional area (CSA). The levels of inflammatory factors were detected using quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Sirtuins1 (SIRT1)/Peroxisome Proliferator-Activated Receptor γ Co-Activator 1α (PGC-1α) and Signal transducer and activator of transcription 3 (STAT3) signaling pathway and the muscle fiber type related proteins in TA muscle after denervation were analyzed by western blot assay.ResultsIntraperitoneal injection of aspirin (20 mg/kg/d) effectively alleviated denervation-induced muscle atrophy. This mainly manifested as follows: The wet weight ratio of TA muscle and muscle fiber CSA of mice treated with aspirin were significantly greater compared with mice treated with normal saline. The level of myosin heavy chain (MHC) increased, and the levels of muscle specific E3 ubiquitin ligase Muscle-specific RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx) were decreased. Mitochondrial vacuolation and autophagy were inhibited, as evidenced by reduced level of autophagy related proteins PINK1, BNIP3, LC3B and Atg7 in mice treated with aspirin compared with mice treated with saline. In addition, aspirin treatment inhibited the slow-to-fast twitch muscle fiber conversion, which were related with triggering the expression of Sirt1 and PGC-1α. Moreover, aspirin reduced the levels of inflammatory factors interleukin-6, interleukin-1β and tumor necrosis factor-α and decreased the activation of STAT3 signaling pathway.ConclusionsThis is the first study to find that aspirin can alleviate denervation-induced muscle atrophy and inhibit the type I-to-type II muscle fiber conversion and mitophagy possibly through regulating the STAT3 inflammatory signaling pathway and Sirt1/PGC-1α signal axis. This study expands our knowledge regarding the pharmacological function of aspirin and provides a novel strategy for prevention and treatment of denervated muscle atrophy.

Dataset Information

LincRNA-p21 alleviates atherosclerosis progression through regulating the miR-221/SIRT1/Pcsk9 axis.

Publications

LincRNA-p21 alleviates atherosclerosis progression through regulating the miR-221/SIRT1/Pcsk9 axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets