Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Curr Vasc Pharmacol. 2020;18(6):652-662. doi: 10.2174/1570161118666200317153124.
Atherosclerosis is the main cause of cardiovascular and cerebrovascular diseases. In advanced atherosclerotic plaque, macrophage apoptosis coupled with inflammatory cytokine secretion promotes the formation of necrotic cores. It has also been demonstrated that the long-noncoding Ribonucleic Acid (lnc RNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), with its potent function on gene transcription modulation, maintains oxidized low-density lipoprotein (ox-LDL)- induced macrophage autophagy (i.e., helps with cholesterol efflux). It also showed that MALAT1 activated Sirtuin 1 (SIRT1), which subsequently inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways. ox-LDL has been used to incubate human myeloid leukemia mononuclear cells (THP-1)-derived macrophages to establish an in vitro foam cell model. Quantitative reverse-transcription polymerase chain reaction and Western blot analyses confirmed the increased expression level of MALAT1 and the autophagy-related protein Microtubuleassociated protein light chain 3 (LC-3), beclin-1. The small interfering RNA study showed a significant decrease in autophagy activity and an increase in apoptotic rate when knocking down MALAT1. Further study demonstrated that MALAT1 inhibited the expression of MAPK and NF-κB (p65) by upregulating SIRT1.
动脉粥样硬化是心血管和脑血管疾病的主要病因。在晚期动脉粥样硬化斑块中，巨噬细胞凋亡加上炎症细胞因子的分泌，促进了坏死核心的形成。研究还表明，长链非编码 RNA（lncRNA）转移相关肺腺癌转录本 1（MALAT1）通过其强大的基因转录调控功能，维持氧化型低密度脂蛋白（ox-LDL）诱导的巨噬细胞自噬（即有助于胆固醇流出）。还表明，MALAT1 激活了沉默信息调节因子 1（SIRT1），随后抑制了丝裂原活化蛋白激酶（MAPK）和核因子 kappa-B（NF-κB）信号通路。用氧化型低密度脂蛋白孵育人髓系白血病单核细胞（THP-1）衍生的巨噬细胞，建立体外泡沫细胞模型。定量逆转录聚合酶链反应和 Western blot 分析证实 MALAT1 和自噬相关蛋白微管相关蛋白轻链 3（LC-3）、beclin-1 的表达水平增加。小干扰 RNA 研究表明，敲低 MALAT1 可显著降低自噬活性并增加细胞凋亡率。进一步的研究表明，MALAT1 通过上调 SIRT1 抑制了 MAPK 和 NF-κB（p65）的表达。
