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The Mechanism Underlying the Regulation of LncRNA-ASLNC18810 Involved in the Abnormal Function of Vascular Endothelial Cell in Atherosclerosis: Its Function as a microRNA (miRNA) Sponge for miR-559

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Abstract

Abnormal function of endothelial cells (ECs) is an important reason for vascular endothelial remodeling and atherosclerotic plaque formation in patients with atherosclerosis (AS). Here, we report for the first time that the vascular ECs with apoptosis resistance phenotype (ARECs) exist in peripheral blood of AS patients. Our research data showed that the switch of regulation modes between HIF-1α and Bax operated by lncRNA-ASLNC18810 is the direct cause for the formation of ARECs. When ASLNC18810 is low or missing, HIF-1α indirectly negatively regulates the Bax in post-transcription through HIF-1α/miR-559/Bax pathway which makes ECs acquire apoptosis resistance and form ARECs. The functional experiments results showed that ASLNC18810 could effectively eliminate the anti-apoptotic properties of ARECs by blocking the HIF-1α/miR559/Bax pathway and maintaining HIF-1α/Bax pathway. In a word, our study shows that ASLNC18810 has full potential to become a biological target for the prevention and treatment of atherosclerotic plaques by regulating ARECs.

Graphical abstract

ASLNC18810 was significantly upregulated in ECs compared to ARECs. With high level of ASLNC18810 in ECs, ASLNC18810 binds to miR-559 as a miRNA sponge and suppresses the inhibition effect of miR-559 on Bax protein, this direct positive transcriptional regulation between HIF-1α and Bax endows the apoptotic property in ECs induced by Ox-LDL. However, with low expression of ASLNC18810 in ARECs, the post-transcriptional regulation of Bax by miR-559 dominates and the indirect negative regulation between HIF-1α and Bax endows the anti-apoptotic property of ARECs. To sum up, low ASLNC18810 expression-mediated switching of HIF-1α/Bax pathway to HIF-1α/miR-559/Bax pathway is the internal reason for ECs to obtain apoptosis resistance and the formation of ARECs under the ox-LDL induction.

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Abbreviations

AS:

Atherosclerosis

ECs:

Endothelial cells

ARECs:

Apoptosis-resistant endothelial cells

Ox-LDL:

Oxidized low-density lipoprotein

LncRNA:

Long non-coding RNA

MiRNA:

MicroRNA

HIF-1α:

Hypoxia inducible factor-1α

Bax:

BCL2-associated X protein

HFD:

High-fat diet

RT-qPCR:

Quantitative reverse transcription PCR

GFP:

Green fluorescent protein

TFBS:

Transcription factor binding site

PI:

Propidium Iodide

MOI:

Multiplicity of infection

DMEM:

Dulbecco’s modification of Eagle’s medium

NC:

Negative control

IF:

Immunofluorescence

cDNA:

Complementary DNA

UTR:

Untranslated regions

EPCs:

Endothelial progenitor cells

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Funding

This work was supported by the National Natural Science Foundation of China (81900293), Shanghai Sailing Program (19YF1431800).

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Author notes

  1. Qian Wang, Yue-Yue Wan, and Na Li have contributed equally to this work and share first authorship

Authors and Affiliations

  1. Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Qian Wang, Pengpai Zhang, Kai Guo & Bo Liu

  2. The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People’s Hospital, Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yue-Yue Wan

  3. Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai, China

    Na Li

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  1. Qian Wang
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  2. Yue-Yue Wan
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Corresponding author

Correspondence to Bo Liu.

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Ethics Approval

All human studies were carried out under informed consent, with data collection approved by the Ethics Committee of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine. All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees.

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The authors declare no competing interests.

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Associate Editor Junjie Xiao oversaw the review of this article

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Wang, Q., Wan, YY., Li, N. et al. The Mechanism Underlying the Regulation of LncRNA-ASLNC18810 Involved in the Abnormal Function of Vascular Endothelial Cell in Atherosclerosis: Its Function as a microRNA (miRNA) Sponge for miR-559. J. of Cardiovasc. Trans. Res. 15, 1010–1023 (2022). https://doi.org/10.1007/s12265-022-10230-3

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  • DOI: https://doi.org/10.1007/s12265-022-10230-3

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