Long non-coding RNA FGD5 antisense RNA 1 targets Baculovirus inhibitor 5 via microRNA-497-5p to alleviate calcific aortic valve disease.

IF 2.1 4区 医学 Q3 HEMATOLOGY Clinical hemorheology and microcirculation Pub Date : 2024-01-01 DOI:10.3233/CH-221692
Jun Wei, XueShuang Zhu, AYu Sun, XiaoTian Yan, Xing Meng, Shenglin Ge
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Abstract

Calcific aortic valve disease (CAVD) is featured by thickening and calcification of the aortic valve. Osteoblast differentiation is a crucial step in valve calcification. Long non-coding RNAs (LncRNAs) participate in the osteogenic differentiation of mesenchymal cells. However, the character of lncRNA FGD5 antisense RNA 1 (FGD5-AS1) in CAVD is uncertain. After collection of human aortic valve tissue samples, detection of FGD5-AS1, microRNA (miR)-497-5p and Baculovirus inhibitor 5 (BIRC5) was conducted. Valve mesenchymal cells were isolated from CAVD patients and induced to differentiate to osteoblasts, and transfected with FGD5-AS1, miR-497-5p and BIRC5 plasmids. Detection of the alkaline phosphatase activity was after osteogenic induction of human aortic valve interstitial cells (hAVICs); Detection of the degree of calcium nodules and osteoblast differentiation markers (RUNX2 and OPN) was conducted. After establishment of a mouse model of CAVD, detection of the thickness of aortic valve leaflets, and the degree of calcification of the valve leaflets, and evaluation of echocardiographic parameters were implemented. Experimental data manifested in CAVD patients, lncRNAFGD5-AS1 and BIRC5 were reduced, but miR-497-5p was elevated; Enhancing lncRNA FGD5-AS1 or repressing miR-497-5p mitigated CAVD by restraining osteogenic differentiation; LncRNA FGD5-AS1 sponged miR-497-5p to target BIRC5; Repressive BIRC5 turned around the therapeutic action of elevated FGD5-AS1 or depressed miR-497-5p on hAVICs; Enhancive FGD5-AS1 in vivo was available to reduce ApoE-/- mouse CAVD induced via high cholesterol diet. All in all, lncRNAFGD5-AS1 targets BIRC5 via miR-497-5p to alleviate CAVD.

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长非编码 RNA FGD5 反义 RNA 1 通过 microRNA-497-5p 靶向 Baculovirus 抑制剂 5,缓解钙化性主动脉瓣疾病。
主动脉瓣钙化病(CAVD)的特征是主动脉瓣增厚和钙化。成骨细胞分化是瓣膜钙化的关键步骤。长非编码 RNA(LncRNA)参与了间充质细胞的成骨分化。然而,lncRNA FGD5反义RNA 1(FGD5-AS1)在CAVD中的特性尚不确定。采集人体主动脉瓣组织样本后,对FGD5-AS1、microRNA(miR)-497-5p和Baculovirus inhibitor 5(BIRC5)进行了检测。从 CAVD 患者体内分离出瓣膜间充质细胞,诱导其分化为成骨细胞,并转染 FGD5-AS1、miR-497-5p 和 BIRC5 质粒。在诱导人主动脉瓣间质细胞(hAVICs)成骨后检测碱性磷酸酶活性;检测钙结节程度和成骨细胞分化标志物(RUNX2和OPN)。建立 CAVD 小鼠模型后,检测主动脉瓣叶厚度和瓣叶钙化程度,并评估超声心动图参数。实验数据显示,在CAVD患者中,lncRNAFGD5-AS1和BIRC5降低,但miR-497-5p升高;增强lncRNA FGD5-AS1或抑制miR-497-5p可通过抑制成骨分化缓解CAVD;增强lncRNA FGD5-AS1或抑制miR-497-5p可通过抑制成骨分化减轻CAVD;LncRNA FGD5-AS1可使miR-497-5p靶向BIRC5;抑制BIRC5可逆转升高的FGD5-AS1或抑制的miR-497-5p对hAVICs的治疗作用;体内增强的FGD5-AS1可降低高胆固醇饮食诱导的载脂蛋白E-/-小鼠CAVD。总之,lncRNAFGD5-AS1通过miR-497-5p靶向BIRC5,从而缓解CAVD。
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来源期刊
CiteScore
4.30
自引率
33.30%
发文量
170
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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