The Pathogenic Role of Long Non-coding RNA H19 in Atherosclerosis via the miR-146a-5p/ANGPTL4 Pathway.
The Pathogenic Role of Long Non-coding RNA H19 in Atherosclerosis via the miR-146a-5p/ANGPTL4 Pathway.
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DOI：
10.3389/fcvm.2021.770163
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发表时间：
2021
影响因子：
3.6
通讯作者：
Ye WC
中科院分区：
文献类型：
--
作者：
Huang SF;Zhao G;Peng XF;Ye WC
异常表达的长链非编码RNA（lncRNA）H19在心血管疾病的发生和发展中具有重要作用;然而，其在动脉粥样硬化中的作用尚不清楚。本研究旨在探讨lncRNA H19在动脉粥样硬化形成中的作用及其机制。本研究的结果表明，lncRNA H19在小鼠血液和主动脉中的表达升高，脂质负载的巨噬细胞和动脉粥样硬化。腺相关病毒（AAV）介导的lncRNA H19过表达显著增加了提供西方饮食的apoE−/−小鼠的动脉粥样硬化斑块面积。lncRNA H19的上调降低了小鼠血液和主动脉以及THP-1细胞中miR-146 a-5 p的表达，但增加了ANGPTL 4的水平。此外，lncRNA H19过表达促进氧化低密度脂蛋白（ox-LDL）诱导的THP-1巨噬细胞中的脂质积累。然而，lncRNA H19的敲除可保护apoE−/−小鼠免受动脉粥样硬化，并降低ox-LDL诱导的THP-1巨噬细胞中脂质的积累。lncRNA H19通过竞争性结合miR-146 a-5 p促进ANGPTL 4的表达，从而促进动脉粥样硬化中的脂质积聚。这些发现共同证明lncRNA H19通过miR-146 a-5 p/ANGPTL 4途径促进脂质在巨噬细胞中的积累并加剧动脉粥样硬化的进展。以lncRNA H19为靶点可能是预防和治疗动脉粥样硬化性疾病的一种理想的治疗方法。
The abnormally expressed long non-coding RNA (lncRNA) H19 has a crucial function in the development and progression of cardiovascular disease; however, its role in atherosclerosis is yet to be known. We aimed to examine the impacts of lncRNA H19 on atherogenesis as well as the involved mechanism. The outcomes from this research illustrated that the expression of lncRNA H19 was elevated in mouse blood and aorta with lipid-loaded macrophages and atherosclerosis. Adeno-associated virus (AAV)-mediated lncRNA H19 overexpression significantly increased the atherosclerotic plaque area in apoE−/− mice supplied with a Western diet. The upregulation of lncRNA H19 decreased the miR-146a-5p expression but increased the levels of ANGPTL4 in mouse blood and aorta and THP-1 cells. Furthermore, lncRNA H19 overexpression promoted lipid accumulation in oxidized low-density lipoprotein (ox-LDL)-induced THP-1 macrophages. However, the knockdown of lncRNA H19 served as a protection against atherosclerosis in apoE−/− mice and lowered the accumulation of lipids in ox-LDL-induced THP-1 macrophages. lncRNA H19 promoted the expression of ANGPTL4 via competitively binding to miR-146a-5p, thus promoting lipid accumulation in atherosclerosis. These findings altogether demonstrated that lncRNA H19 facilitated the accumulation of lipid in macrophages and aggravated the progression of atherosclerosis through the miR-146a-5p/ANGPTL4 pathway. Targeting lncRNA H19 might be an auspicious therapeutic approach for preventing and treating atherosclerotic disease.
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影响因子：
4.6
作者：
Coffey, Alisha R.;Kanke, Matt;Bennett, Brian J.
通讯作者：
Bennett, Brian J.
LncRNA-FA2H-2-MLKL通路在动脉粥样硬化中的作用
影响因子：
12.4
作者：
Guo, Feng-Xia;Wu, Qian;Wang, Qian
通讯作者：
Wang, Qian
影响因子：
6
作者：
Li, Xiaojiaoyang;Liu, Runping;Zhou, Huiping
通讯作者：
Zhou, Huiping
DOI：
10.1161/atvbaha.120.314333
发表时间：
2020-10
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
de Yébenes VG;Briones AM;Martos-Folgado I;Mur SM;Oller J;Bilal F;González-Amor M;Méndez-Barbero N;Silla-Castro JC;Were F;Jiménez-Borreguero LJ;Sánchez-Cabo F;Bueno H;Salaices M;Redondo JM;Ramiro AR
通讯作者：
Ramiro AR
影响因子：
64.5
作者：
Kopp F;Mendell JT
通讯作者：
Mendell JT