NEAT1 promotes the repair of abdominal aortic aneurysms of endothelial progenitor cells via regulating miR-204-5p/Ang-1

Chao Shi; Chongwen Shen; Ge Liu; Shaofeng Yang; Fenglin Ye; Jinjin Meng; Youmin Pan

NEAT1 promotes the repair of abdominal aortic aneurysms of endothelial progenitor cells via regulating miR-204-5p/Ang-1

Am J Transl Res. 2021 Apr 15;13(4):2111-2126. eCollection 2021.

Authors

Chao Shi¹, Chongwen Shen¹, Ge Liu¹, Shaofeng Yang¹, Fenglin Ye¹, Jinjin Meng¹, Youmin Pan²

Affiliations

¹ Department of Cardiothoracic Surgery, The First Affiliated Hospital of Bengbu Medical College Bengbu, China.
² Department of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei Province, China.

PMID: 34017378
PMCID: PMC8129351

Abstract

Purpose: To clarify the regulatory effect of Nuclear-enriched abundant transcript 1 (NEAT1) on abdominal aortic aneurysm (AAA) model rats and isolated endothelial progenitor cells (EPCs).

Methods: The AAA rat model was established by CaCl₂ stimulation, and overexpressed NEAT1 was injected into rats through tail vein. Abdominal aorta lesions and numbers of EPCs in tissues and peripheral blood were examined by hematoxylin-eosin, immunofluorescence and flow cytometry. The extracted EPCs were identified by microscopy, DiI-ac-LDL staining and flow cytometry. Effect of overexpressed/silencing NEAT1 on the viability, migration, tube formation and VEGF content of EPCs was investigated by MTT-, wound-healing, tube formation assays and ELISA, respectively. The expressions of NEAT1, miR-204-5p, Angiopoietin-1 (Ang-1)/ERK pathway were determined by qRT-PCR and Western blot as needed. The targeting relationships between NEAT1 and miR-204-5p, and miR-204-5p and Ang-1 were predicted on starBase, TargetScan and confirmed by dual-luciferase experiments. The mutual regulation effect was studied through rescue experiments.

Results: Overexpressed NEAT1 not only reduced inflammatory infiltration and increased the number of EPCs in abdominal aorta and peripheral blood, but also promoted the viability, migration, tube formation of EPCs, increased VEGF content and upregulated the expression of the Ang-1/ERK pathway in EPCs. However, silencing NEAT1 produced opposite results. NEAT1 targeting miR-204-5p inhibited the functional effects of miR-204-5p on of EPCs. Overexpressed/silencing Ang-1 partially reversed the effects of NEAT1 or miR-204-5p on the characteristics of EPCs.

Conclusion: NEAT1 competitively binds with miR-204-5p and up-regulates Ang-1 expression in EPCs to effectively improve the proliferation, migration and angiogenesis of EPCs.

Keywords: Angiopoietin-1; Nuclear-enriched abundant transcript 1; abdominal aortic aneurysm; endothelial progenitor cells; miR-204-5p.