1. miR-33-5p knockdown attenuates abdominal aortic aneurysm progression via promoting target adenosine triphosphate-binding cassette transporter A1 expression and activating the PI3K/Akt signaling pathway
- Author
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Kai-Xiong Qing, Yancui Zhu, Yaoyu Feng, Jin Wang, Shengbin Han, Lingfeng Zhao, and Jian Huang
- Subjects
Male ,THP-1 Cells ,030204 cardiovascular system & hematology ,chemistry.chemical_compound ,0302 clinical medicine ,Aorta, Abdominal ,0303 health sciences ,Gene knockdown ,biology ,General Medicine ,Middle Aged ,Abdominal aortic aneurysm ,Up-Regulation ,Cholesterol ,Gene Knockdown Techniques ,Disease Progression ,Cytokines ,lipids (amino acids, peptides, and proteins) ,Female ,Inflammation Mediators ,Cardiology and Cardiovascular Medicine ,Safety Research ,medicine.drug ,ATP Binding Cassette Transporter 1 ,Signal Transduction ,miR-33 ,Proinflammatory cytokine ,03 medical and health sciences ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,030304 developmental biology ,Aged ,Advanced and Specialized Nursing ,business.industry ,Transporter ,medicine.disease ,Adenosine ,MicroRNAs ,chemistry ,ABCA1 ,Case-Control Studies ,Cancer research ,biology.protein ,Phosphatidylinositol 3-Kinase ,business ,Adenosine triphosphate ,Proto-Oncogene Proteins c-akt ,Aortic Aneurysm, Abdominal ,Foam Cells - Abstract
Purpose: The aim of this study was to investigate the role of miR-33-5p in abdominal aortic aneurysm progression, which regulated adenosine triphosphate-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux and lipid accumulation in THP-1 macrophage-derived foam cells through the PI3K/Akt pathway. Methods: Quantitative reverse transcription polymerase chain reaction was used to evaluate the expression level of miR-33-5p and ABCA1 mRNA in abdominal aortic aneurysm patient and normal person tissues. The relationship between miR-33-5p and ABCA1 was examined by dual luciferase report assay. High-performance liquid chromatography was used to evaluate the levels of cholesterol contents. Cholesterol efflux detection was performed by liquid scintillator. The expression of inflammatory cytokines was detected by quantitative reverse transcription polymerase chain reaction. Western blot was applied to determine the expression levels of ABCA1, PI3K (p-PI3K), and Akt (p-Akt). Results: The quantitative reverse transcription polymerase chain reaction analysis results revealed miR-33-5p overexpression in abdominal aortic aneurysm tissues, but the expression level of ABCA1 was lower in abdominal aortic aneurysm tissues than non-abdominal aortic aneurysm tissues. Subsequently, the dual luciferase report gene assay confirmed that ABCA1 was a target of miR-33-5p, and miR-33-5p-negative regulated ABCA1 expression. Moreover, the expression levels of p-PI3K, p-Akt, and ABCA1 were decreased in THP-1 cell transferred with ABCA1 siRNA, but knockdown of miR-33-5p had an opposite effect. Furthermore, knockdown of miR-33-5p decreased the expression of MMP-2, MMP-9, TNF-α, total cellular cholesterol, and promoted cholesterol efflux in THP-1-derived foam cells. Importantly, LY294002 (PI3K inhibitor) or si-ABCA1 completely inhibited the stimulatory effects of miR-33-5p inhibitor. Conclusion: This study has found that knockdown of miR-33-5p induced ABCA1 expression and promoted inflammatory cytokines and cholesterol efflux likely via activating the PI3K/Akt signaling pathway.
- Published
- 2019