Knockdown of lncRNA ENST00000609755.1 Confers Protection Against Early oxLDL-Induced Coronary Heart Disease

Yi Sun; Shuna Huang; Chunyu Wan; Qishuang Ruan; Xiaoxu Xie; Donghong Wei; Guobo Li; Shaowei Lin; Huangyuan Li; Siying Wu

doi:10.3389/fcvm.2021.650212

Knockdown of lncRNA ENST00000609755.1 Confers Protection Against Early oxLDL-Induced Coronary Heart Disease

Front Cardiovasc Med. 2021 May 21:8:650212. doi: 10.3389/fcvm.2021.650212. eCollection 2021.

Authors

Yi Sun¹, Shuna Huang², Chunyu Wan¹, Qishuang Ruan³, Xiaoxu Xie¹, Donghong Wei¹, Guobo Li¹, Shaowei Lin¹, Huangyuan Li¹, Siying Wu¹

Affiliations

¹ School of Public Health, Fujian Medical University, Fuzhou, China.
² Department of Clinical Research and Translation Center Office, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
³ Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou, China.

Abstract

Background: 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. Methods: 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. Results: A total of 320 lncRNAs were found dysregulated in CHD patients (fold change> 2, p < 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 in vitro attenuated the effects of oxLDL on HCAECs morphology, proliferation, and apoptosis. Conclusion: 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.

Keywords: coronary heart disease; environmental factors; human coronary artery endothelial cells; long non-coding RNA; oxidized low-density lipoprotein.