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Long Noncoding RNA-CERNA1 Stabilized Atherosclerotic Plaques in apolipoprotein E−/− Mice

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Abstract

Atherosclerosis is predicted to be the primary cause of death in the world by 2020. Changes in atherosclerotic plaque composition will lead to acute coronary syndromes. Although the studies on the molecular mechanisms of long noncoding RNA (lncRNA) are in-depth in molecular and cell levels, the in vivo research which studied the knowledge about lncRNAs in the regulation of plaque composition is still sparse. In this study, in order to investigate how a new lncRNA, CERNA1, regulates the composition of atherosclerotic plaques, we overexpressed CERNA1 in apolipoprotein E−/− (Apo E−/−) mice and analyzed the role of CERNA1 in atherosclerotic plaque stabilization. The results showed that CERNA1 inhibited the apoptosis of VSMCs and anti-inflammatory macrophages through increasing API5 level and further stabilized the atherosclerotic plaques. This discovery provided a novel therapeutic target for atherosclerosis.

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Abbreviations

Apo E −/− :

apolipoprotein E −/−

API5:

Apoptosis inhibitor 5

HUVECs:

Human umbilical vein endothelial cells

lncRNA:

Long noncoding RNA

MMP2/9:

Matrix metalloproteinase 2/9

VECs:

Vascular endothelial cells

VSMCs:

Vascular smooth muscle cells

oxLDL:

Oxidized low-density lipoprotein

TUNEL:

Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling

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Acknowledgements

Special thanks to Yifeng Li for his technical support.

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 91539105, 81321061, 31270877, and 31070735), Shandong Excellent Young Scientist Award Fund (No. BS2013SW001), the Science and Technology Development Project of Shandong Province (2014GSF118158), Specialized Research Fund for the Doctoral Program of Higher Education (No. 20120131130010), and the National 973 Research Project (No. 2011CB503906).

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Authors and Affiliations

  1. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People’s Republic of China

    Wei Lu, Xiaoying He, Le Su & Junying Miao

  2. Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People’s Republic of China

    Wei Lu

  3. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, 250012, People’s Republic of China

    Junying Miao

  4. Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, People’s Republic of China

    Junying Miao

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  1. Wei Lu
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Correspondence to Junying Miao.

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The authors declare that they have no conflict of interest.

Ethical Approval

In this study, all animal experiments and all procedures were performed in accordance with the ARRIVE guidelines and approved by the ethics committee in Shandong University, China. And no human studies were carried out by the authors for this article.

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Associate Editor Joost Sluijter oversaw the review of this article

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Lu, W., He, X., Su, L. et al. Long Noncoding RNA-CERNA1 Stabilized Atherosclerotic Plaques in apolipoprotein E−/− Mice. J. of Cardiovasc. Trans. Res. 12, 425–434 (2019). https://doi.org/10.1007/s12265-019-09883-4

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