Expression status and clinical significance of lncRNA APPAT in the progression of atherosclerosis

Fanming Meng; Jie Yan; Qiongshan Ma; Yunjuan Jiao; Luyang Han; Jing Xu; Fan Yang; Junwen Liu

doi:10.7717/peerj.4246

Expression status and clinical significance of lncRNA APPAT in the progression of atherosclerosis

PeerJ. 2018 Jan 17:6:e4246. doi: 10.7717/peerj.4246. eCollection 2018.

Authors

Fanming Meng¹, Jie Yan², Qiongshan Ma¹, Yunjuan Jiao¹, Luyang Han¹, Jing Xu³, Fan Yang⁴, Junwen Liu¹

Affiliations

¹ Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, People's Republic of China.
² Department of Forensic Science, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, People's Republic of China.
³ Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, People's Republic of China.
⁴ Department of Internal Neurology, Tongliao KEQU First Hospital, Tongliao, People's Republic of China.

Abstract

Background: Long non-coding RNAs (lncRNAs) have been reported to modulate cardiovascular diseases, and expression dynamics of lncRNAs in the bloodstream were proposed to be potential biomarkers for clinical diagnosis. However, few cardiovascular diseases-related circulating lncRNAs were identified and their prediction power has not been investigated in depth. Here we report a new circulating lncRNA, atherosclerotic plaque pathogenesis associated transcript (APPAT), and evaluated its role and predicting ability in atherosclerotic development.

Methods: APPAT was analyzed and screened by high-throughput sequencing, and then detected in vitro and in vivo. Immunofluorescence-fluorescence in situ hybridization (IF-FISH) was utilized to explore distribution and subcellular location of APPAT. The expressing alteration of APPAT in samples of healthy and pathological coronary artery was explored further. We also assessed the level of circulating APPAT in blood samples from healthy individuals, and patients with angina pectoris (AP) or myocardial infarction (MI). Additionally, we predicted and validated microRNA targets of APPAT, then showed the expression level of a candidate target which was primarily measured in human VSMCs cell line, coronary artery, and blood samples. Lastly, we examined the potential indicating ability of APPAT for the risk of AP or MI.

Results: APPAT showed significant reduction in ox-LDL treated human VSMCs in vitro. It enriched in contractile VSMCs of artery tunica media and mainly existed in cytoplasm. Significant down-regulation of APPAT was found in coronary artery samples with severe stenosis. More importantly, we observed decreased expression of APPAT in blood samples accompanying disease progression. ROC and correlation analyses further verified the relatively high predicting ability of APPAT. We also observed the predicted miRNA exhibited opposite expression direction to that of APPAT.

Conclusions: This study revealed that circulating lncRNA-APPAT may perform an important function and have some indicating ability on the development of atherosclerosis.

Keywords: Atherosclerosis; Biomarker; Cardiovascular disease; Circulating lncrna; High-throughput sequencing.

Associated data

figshare/10.6084/m9.figshare.5446705.v1

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant number 81270371, 81770462], and the Science and Technology Program of Hunan Province (2015RS4014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.