Inhibition of circ_0000231 suppresses oxidized low density lipoprotein-induced apoptosis, autophagy and inflammation in human umbilical vein endothelial cells by regulating miR-590-5p/PDCD4 axis.
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引用次数: 0
Abstract
Background: Circular RNAs (circRNAs) are the emerging informative RNAs, involved in cardiovascular diseases including atherosclerosis (AS). Endothelial injury is the initial qualitative change of AS. Thus, the objective of this study was to confirm the dysregulation and mechanism of circ_0000231 in cell model of AS at early stage in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (ox-LDL).
Methods: The expression of circ_0000231, miR-590-5p and programmed cell death 4 (PDCD4) was detected using real-time quantitative PCR and western blot. Cell injury was measured with MTT, flow cytometry, caspase-3 activity assay and enzyme-linked immunosorbent assay (ELISA). The interaction among circ_0000231, miR-590-5p and PDCD4 was validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assays.
Results: Stress ox-LDL decreased cell viability, and increased apoptosis rate and caspase-3 activity in HUVECs in a dose- and time-dependent manner in concomitant with promotions of interleukin-6, interleukin-1β, tumor necrosis factor-α, LC3-II/I and Beclin-1 levels. Besides, circ_0000231 and PDCD4 expressions were upregulated, and miR-590-5p was downregulated in ox-LDL-stimulated HUVECs. Functionally, knockdown of circ_0000231 and overexpression of miR-590-5p could suppress ox-LDL-elicited above effects on apoptosis, autophagy and inflammatory response, accompanied with PDCD4 downregulation. Physically, miR-590-5p could directly interact with circ_0000231 and PDCD4.
Conclusion: Downregulation of circ_0000231 suppresses HUVECs from ox-LDL-induced injury partially through regulating miR-590-5p/PDCD4 axis via competing endogenous RNA mechanism, showing a novel potential target for the pathology and treatment of endothelial injury in AS.
期刊介绍：
Clinical Hemorheology and Microcirculation, a peer-reviewed international scientific journal, serves as an aid to understanding the flow properties of blood and the relationship to normal and abnormal physiology. The rapidly expanding science of hemorheology concerns blood, its components and the blood vessels with which blood interacts. It includes perihemorheology, i.e., the rheology of fluid and structures in the perivascular and interstitial spaces as well as the lymphatic system. The clinical aspects include pathogenesis, symptomatology and diagnostic methods, and the fields of prophylaxis and therapy in all branches of medicine and surgery, pharmacology and drug research.
The endeavour of the Editors-in-Chief and publishers of Clinical Hemorheology and Microcirculation is to bring together contributions from those working in various fields related to blood flow all over the world. The editors of Clinical Hemorheology and Microcirculation are from those countries in Europe, Asia, Australia and America where appreciable work in clinical hemorheology and microcirculation is being carried out. Each editor takes responsibility to decide on the acceptance of a manuscript. He is required to have the manuscript appraised by two referees and may be one of them himself. The executive editorial office, to which the manuscripts have been submitted, is responsible for rapid handling of the reviewing process.
Clinical Hemorheology and Microcirculation accepts original papers, brief communications, mini-reports and letters to the Editors-in-Chief. Review articles, providing general views and new insights into related subjects, are regularly invited by the Editors-in-Chief. Proceedings of international and national conferences on clinical hemorheology (in original form or as abstracts) complete the range of editorial features.
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