Sun Yi, Huang Shuna, Wan Chunyu, Ruan Qishuang, Xie Xiaoxu, Wei Donghong, Li Guobo, Lin Shaowei, Li Huangyuan, Wu Siying
School of Public Health, Fujian Medical University, Fuzhou, China.
Department of Clinical Research and Translation Center Office, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Front Cardiovasc Med. 2021 May 21;8:650212. doi: 10.3389/fcvm.2021.650212. eCollection 2021.
This study investigated the association between long non-coding RNAs (lncRNAs) and coronary heart disease (CHD) and further elucidated the potential biological roles of lncRNAs in CHD pathogenesis. A case-control study (590 patients and 590 controls) was conducted from February 2017 and March 2019 in Fuzhou, China. Environmental factors were investigated using questionnaires and physical examinations. Five representative lncRNAs were screened using lncRNA microarray (peripheral blood in 5 cases and 5 controls) and further verified by quantitative real-time polymerase chain reaction (peripheral blood leukocyte in 100 cases and 100 controls). Oxidized low-density lipoprotein (oxLDL) was used to induce a human coronary artery endothelial cell (HCAECs) injury model, and loss of function was used to elucidate the role of lncRNA ENST00000609755.1 (lnc-MICALL2-2) in oxLDL-induced HCAECs injury. A total of 320 lncRNAs were found dysregulated in CHD patients (fold change> 2, < 0.05). The results of a discovery microarray, population verification and HCAEC experiments suggested the lnc-MICALL2-2 is upregulated in CHD subjects and in an oxLDL-induced HCAECs injury model. Conversely, lnc-MICALL2-2 inhibition attenuated the effects of oxLDL on HCAECs morphology, proliferation, and apoptosis. Elevated expression of lnc-MICALL2-2 is an independent risk factor for CHD, and knockdown subsequently confers protection against early pathological processes of oxLDL-induced CHD.
本研究调查了长链非编码RNA（lncRNAs）与冠心病（CHD）之间的关联，并进一步阐明了lncRNAs在冠心病发病机制中的潜在生物学作用。2017年2月至2019年3月在中国福州进行了一项病例对照研究（590例患者和590例对照）。通过问卷调查和体格检查对环境因素进行了调查。使用lncRNA微阵列（5例患者和5例对照的外周血）筛选了5种代表性lncRNAs，并通过定量实时聚合酶链反应（100例患者和100例对照的外周血白细胞）进一步验证。使用氧化型低密度脂蛋白（oxLDL）诱导人冠状动脉内皮细胞（HCAECs）损伤模型，并通过功能缺失研究lncRNA ENST00000609755.1（lnc-MICALL2-2）在oxLDL诱导的HCAECs损伤中的作用。共发现320种lncRNAs在冠心病患者中表达失调（倍数变化>2，<0.05）。发现微阵列、人群验证和HCAEC实验结果表明，lnc-MICALL2-2在冠心病患者和oxLDL诱导的HCAECs损伤模型中上调。相反，lnc-MICALL2-2抑制减弱了oxLDL对HCAECs形态、增殖和凋亡的影响。lnc-MICALL2-2表达升高是冠心病的独立危险因素，敲低该基因随后可对oxLDL诱导的冠心病早期病理过程起到保护作用。
