Department of Cardiology, Tianjin Chest Hospital, Tianjin, China.
Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin, China.
Cell Cycle. 2021 Sep;20(17):1642-1652. doi: 10.1080/15384101.2021.1951940. Epub 2021 Aug 12.
Coronary atherosclerosis (CAS) is a major cause of cardiovascular disease. Long non-coding RNAs (lncRNAs) have been implicated as novel biomarkers in coronary artery disease (CAD). APOA1 antisense RNA (APOA1-AS) was proven to show high expression during atherosclerotic development, but no report has uncovered the detailed mechanism of APOA1-AS in CAS. Thus, this paper aims to explore the role of APOA1-AS in CAS. Vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL) to mimic atherosclerosis-like injury. Quantitative real-time PCR (RT-qPCR) and western blot analysis analyzed gene expression. Cell counting kit-8 (CCK-8), wound healing assay, and flow cytometry were implemented to assess the function of APOA1-AS in modulating pathological phenotype of VSMCs. Results demonstrated that APOA1-AS was notably up-regulated in ox-LDL treated VSMCs (ox-LDL-VSMCs). The deficiency of APOA1-AS hindered proliferation and migration and stimulated apoptosis in ox-LDL-VSMCs. Mechanistically, APOA1-AS recruited TATA-box binding protein associated factor 15 (TAF15) protein to stabilized SMAD family member 3 (SMAD3) mRNA and activate the TGF-β/SMAD3 signaling pathway. In conclusion, APOA1-AS contributed to proliferation and migration and repressed apoptosis of VSMCs through TAF15-mediated SMAD3 mRNA stabilization, indicating that APOA1-AS could be a promising target for CAS.
冠状动脉粥样硬化（CAS）是心血管疾病的主要原因。长链非编码 RNA（lncRNA）已被认为是冠心病（CAD）的新型生物标志物。载脂蛋白 A1 反义 RNA（APOA1-AS）在动脉粥样硬化发展过程中表现出高表达，但尚无报道揭示 APOA1-AS 在 CAS 中的详细机制。因此，本文旨在探讨 APOA1-AS 在 CAS 中的作用。用氧化低密度脂蛋白（ox-LDL）处理血管平滑肌细胞（VSMCs）以模拟动脉粥样硬化样损伤。定量实时 PCR（RT-qPCR）和 Western blot 分析分析基因表达。细胞计数试剂盒-8（CCK-8）、划痕愈合试验和流式细胞术用于评估 APOA1-AS 调节 VSMCs 病理表型的功能。结果表明，APOA1-AS 在 ox-LDL 处理的 VSMCs（ox-LDL-VSMCs）中明显上调。APOA1-AS 的缺乏抑制了 ox-LDL-VSMCs 的增殖和迁移，并刺激了凋亡。在机制上，APOA1-AS 招募 TATA 框结合蛋白相关因子 15（TAF15）蛋白稳定 SMAD 家族成员 3（SMAD3）mRNA，并激活 TGF-β/SMAD3 信号通路。总之，APOA1-AS 通过 TAF15 介导的 SMAD3 mRNA 稳定促进 VSMCs 的增殖和迁移，并抑制凋亡，表明 APOA1-AS 可能是 CAS 的一个有前途的靶点。
