MicroRNA-29a attenuates angiotensin-II induced-left ventricular remodeling by inhibiting collagen, TGF-β and SMAD2/3 expression
MicroRNA-29a attenuates angiotensin-II induced-left ventricular remodeling by inhibiting collagen, TGF-β and SMAD2/3 expression
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MicroRNA-29a 通过抑制胶原蛋白、TGF-β 和 SMAD2/3 表达来减弱血管紧张素 II 诱导的左心室重塑
DOI：
10.11909/j.issn.1671-5411.2020.02.008
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发表时间：
2020-02
影响因子：
2.5
通讯作者：
Hao XUE
中科院分区：
文献类型：
--
作者：
Si-Jin ZHANG;Cui-Juan YUN;Jie LIU;Si-Yu YAO;Yao LI;Miao WANG;Chi WANG;Yong-Yi BAI;Hao XUE
背景：左心室重构是高血压最常见的靶器官损害。我们先前的研究发现，血浆microRNA-29a(miR-29a)水平与高血压患者的左室重构有关。然而，miR-29a与LV重构之间的因果关系尚不清楚。因此，本研究旨在探讨miR-29a在左心室重构中的调控机制。方法：通过尾静脉注射miR-29a模拟病毒和慢病毒抑制剂，分别建立高表达和基因敲除的miR-29a小鼠模型。然后用血管紧张素-II(AngII)皮下注射血管紧张素-II(AngII)胶囊的方法诱导小鼠左室重构，持续4周。以血管紧张素转换酶诱导的小鼠左室重构为模型组(n=9)。6只年龄匹配的雄性SPF C57/BL6J小鼠(6~8周龄)以生理盐水为载体进行处理(n=6)。在体内，过表达miR-29a可改善血管紧张素Ⅱ诱导的左心室重构，而敲除miR-29a则加重左心室重构。同时，我们观察到过表达miR-29a的小鼠抑制心脏横截面积增加，而敲除miR-29a的小鼠心脏横截面积增加，表明miR-29a对心肌肥大有拮抗作用。进一步研究发现，过表达miR-29a可抑制心肌组织中I型和III型胶原的含量，且随着I型和III型胶原表达下调，转化生长因子-β(TGFR-β)和磷酸化Smad2/3的表达减少。结论过表达miR-29a通过抑制胶原沉积、转化生长因子-β和磷酸化Smad2/3的表达而减轻左室重构。因此，干预miR-29a可能成为减轻左室重构的治疗靶点。
Background Left ventricular (LV) remodeling is the most common target organ damage in hypertension. Previously, our study found that plasma microRNA-29a (miR-29a) level was associated with the LV remodeling in hypertensive patients. However, the causal relationship between miR-29a and LV remodeling remains unknown. Thus, the aim of this study was to investigate the regulation mechanism of miR-29a in LV remodeling. Methods & Results Overexpression and knockdown miR-29a mice were generated by tail-intravenous injection of miR-29a-mimic and inhibitor lentivirus for one week respectively. Then the mice were subjected to angiotensin-II (AngII) induced LV remodeling by subcutaneous AngII capsule osmotic pumping into AngII for four weeks. AngII-induced LV remodeling mice as the model group (n = 9). Age-matched male SPF C57/BL6J mice (6–8 weeks old) were treated with the pumping of saline as a vehicle (n = 6). In vivo, overexpression miR-29a ameliorated AngII-induced LV remodeling, while knockdown miR-29a deteriorated LV remodeling. Simultaneously, we observed that overexpression miR-29a mice inhibited but knockdown miR-29a mice increased cardiac cross-sectional area, indicating that miR-29a has an antagonistic effect on cardiac hypertrophy. Further studies found that overexpression miR-29a inhibited the content of the LV collagen including collagen I and III. Moreover, the expression of transforming growth factor-β (TGF-β) and phosphorylated SMAD2/3 decreased with the down-regulation of collagen I and III in overexpression miR-29a mice. Conclusions Our finding indicates that overexpression miR-29a attenuates LV remodeling by inhibiting collagen deposition, TGF-β, and phosphorylated SMAD2/3 expression. Thus, intervention miR-29a may be a therapeutic target for attenuating LV remodeling
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影响因子：
24
作者：
Roncarati, Roberta;Anselmi, Chiara Viviani;Condorelli, Gianluigi
通讯作者：
Condorelli, Gianluigi
DOI：
10.1073/pnas.0805038105
发表时间：
2008-09-02
影响因子：
11.1
作者：
van Rooij, Eva;Sutherland, Lillian B.;Olson, Eric N.
通讯作者：
Olson, Eric N.
DOI：
--
发表时间：
1994
期刊：
The New England journal of medicine
影响因子：
--
作者：
W. A. Border;N. Noble
通讯作者：
W. A. Border;N. Noble
影响因子：
4
作者：
Li, Qing;Song, Xiao-Wei;Jing, Qing
通讯作者：
Jing, Qing
影响因子：
6
作者：
H. Xue;Shu-xia Wang;Hu Wang;K. Sun;Xiao-dong Song;Weili Zhang;Chun-yan Fu;Yun-feng Han;R. Hui
通讯作者：
H. Xue;Shu-xia Wang;Hu Wang;K. Sun;Xiao-dong Song;Weili Zhang;Chun-yan Fu;Yun-feng Han;R. Hui