MicroRNA‑1929‑3p participates in murine cytomegalovirus‑induced hypertensive vascular remodeling through Ednra/NLRP3 inflammasome activation.

MicroRNA‑1929‑3p participates in murine cytomegalovirus‑induced hypertensive vascular remodeling through Ednra/NLRP3 inflammasome activation.
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MicroRNA-1929-3p通过Ednra/NLRP3炎症小体激活参与小鼠巨细胞病毒诱导的高血压血管重塑

DOI:
10.3892/ijmm.2020.4829
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发表时间:
2021-03
影响因子:
5.4
通讯作者:
He F
He F
中科院分区:
医学3区
文献类型:
--
作者:
Zhou W;Xi D;Shi Y;Wang L;Zhong H;Huang Z;Liu Y;Tang Y;Lu N;Wang Y;Zhang Z;Pei J;Tang N;He F

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microRNAs(miRNAs)通过介导人巨细胞病毒(HCMV)对血管系统的影响,在原发性高血压(EH)血管重构的发生发展中发挥重要作用。因此,本研究的目的是研究小鼠巨细胞病毒(MCMV)感染对小鼠血压和血管功能的影响,以阐明miR-1929- 3 p在此过程中的作用。用MCMV Smith株感染7月龄C57 BL/6 J小鼠,检测MCMV DNA、IgG和IgM。随后,通过颈动脉测量血压,并通过苏木精-伊红和Masson三色染色评价主动脉的形态学变化。用腺相关病毒包装的载体转染miR-1929- 3 p,观察其对血管结构的影响。用比色法测定一氧化氮(NO)和内皮型一氧化氮合酶(NOS)水平。采用免疫组化和蛋白质印迹法检测血管重塑和NLRP 3炎症相关蛋白的表达。ELISA法检测内皮素-1(ET-1)、白细胞介素-1β(IL-1 β)和白细胞介素-18(IL-18)。结果表明,MCMV感染可引起血压升高、血管重构、内皮细胞损伤和miR-1929- 3 p表达下调。然而,这些作用被miR-1929- 3 p过表达减轻,其下调内皮素A受体(Ednra)和NLRP 3炎性体,以及内皮损伤和血管重塑相关基因。综上所述,本研究的结果表明,miR-1929- 3 p的过表达可能通过ET-1/Ednra灭活NLRP 3炎性体来改善MCMV诱导的血管重塑。
MicroRNAs (miRNAs) play an important role in the development of vascular remodeling in essential hypertension (EH) by mediating the effects of human cytomegalovirus (HCMV) on the vascular system. Therefore, the aim of the present study was to investigate the effects of murine cytomegalovirus (MCMV) infection on blood pressure and vascular function in mice, in order to elucidate the role of miR-1929-3p in this process. For model development, 7-month-old C57BL/6J mice were infected with the Smith strain of MCMV, and MCMV DNA, IgG and IgM were detected. Subsequently, blood pressure was measured via the carotid artery, and the morphological changes of the aorta were evaluated by hematoxylin and eosin and Masson's trichrome staining. miR-1929-3p transfection was performed using an adeno-associated virus packaged vector and the changes in vascular structure were then observed. The levels of nitric oxide (NO) and endothelial NO synthase were also assessed with colorimetry. Vascular remodeling and expression of NLRP3 inflammasome pathway-related proteins were detected by immunohistochemistry and western blotting. Endothelin-1 (ET-1), interleukin (IL)-1β and IL-18 were assayed by ELISA. The results revealed that MCMV infection increased the blood pressure, promoted vascular remodeling, caused endothelial cell injury, and downregulated miR-1929-3p. However, these effects were alleviated by miR-1929-3p overexpression, which downregulated endothelin A receptor (Ednra) and NLRP3 inflammasome, as well as endothelial injury- and vascular remodeling-related genes. Taken together, the findings of the present study indicated that overexpression of miR-1929-3p may improve MCMV-induced vascular remodeling, possibly via the deactivation of the NLRP3 inflammasome by ET-1/Ednra.
DOI: 10.1038/s41371-018-0061-2
发表时间: 2018-06
影响因子: 2.7
作者:
Hijmans JG;Diehl KJ;Bammert TD;Kavlich PJ;Lincenberg GM;Greiner JJ;Stauffer BL;DeSouza CA
通讯作者: DeSouza CA
DOI: 10.1111/imr.12286
发表时间: 2015-05
影响因子: 8.7
作者:
Elliott EI;Sutterwala FS
通讯作者: Sutterwala FS
DOI: 10.1016/j.pharmthera.2018.10.001
发表时间: 2019-03
影响因子: 13.5
作者:
D'Orléans-Juste P;Akide Ndunge OB;Desbiens L;Tanowitz HB;Desruisseaux MS
通讯作者: Desruisseaux MS
DOI: 10.1161/01.hyp.0000153051.56460.6a
发表时间: 2005-02-01
期刊: HYPERTENSION
影响因子: 8.3
作者:
Elmarakby, AA;Loomis, ED;Pollock, DM
通讯作者: Pollock, DM
DOI: 10.1161/hypertensionaha.119.12619
发表时间: 2019-05-01
期刊: HYPERTENSION
影响因子: 8.3
作者:
Huo, Ku-Geng;Richer, Chantal;Schiffrin, Ernesto L.
通讯作者: Schiffrin, Ernesto L.