Nebivolol Induces Distinct Changes in Profibrosis MicroRNA Expression Compared With Atenolol, in Salt-Sensitive Hypertensive Rats
Nebivolol Induces Distinct Changes in Profibrosis MicroRNA Expression Compared With Atenolol, in Salt-Sensitive Hypertensive Rats
复制标题
与阿替洛尔相比，奈必洛尔在盐敏感性高血压大鼠中引起促纤维化 MicroRNA 表达的明显变化
DOI：
10.1161/hypertensionaha.111.00892
复制
发表时间：
2013-05-01
期刊：
影响因子：
8.3
通讯作者：
Birnbaum, Yochai
中科院分区：
文献类型：
--
作者：
Ye, Hongmei;Ling, Shukuan;Birnbaum, Yochai
奈必洛尔是一种选择性β 1受体阻滞剂，具有一氧化氮增强作用。MicroRNA是一种小的非编码RNA分子，可下调基因表达。我们比较了奈必洛尔和阿替洛尔（第一代β 1选择性阻滞剂）对高血压啮齿动物模型左心室肥厚、纤维化、功能和microRNA表达的影响。Dahl盐敏感大鼠接受低盐食物（对照）或AIN-76 A高盐（8%NaCl）饮食，并随机分配至媒介物（高盐）、奈必洛尔（20 mg/kg/天）或阿替洛尔（50 mg/kg/天），持续8周。高盐诱导左心室肥厚和纤维化，并降低miR-27 a、-29 a和-133 a的表达。奈博洛尔比阿替洛尔更能减轻左心室收缩功能恶化、重构和纤维化，尽管对心率和血压的影响相似。奈必洛尔（而非阿替洛尔）可阻止高盐诱导的miR-27 a和-29 a减少。奈必洛尔和阿替洛尔同样减弱了miR-133 a的降低。体外过表达miR-27 a、-29 a和-133 a可抑制心肌细胞肥大并降低胶原蛋白表达。miR-27 a和-29 a都靶向Sp1，而miR-133 a靶向Cdc 42。Sp1和Cdc 42的药理学抑制降低心肌纤维化和肥大。我们的数据支持盐诱导的高血压中的差异microRNA表达谱。奈必洛尔比阿替洛尔更能显着减轻心脏重塑、肥大和纤维化。这些作用与高血压诱导的miR-27 a和-29 a（随后Sp1表达降低）和miR-133 a（随后Cdc 42降低）降低的减弱有关。（高血压。2013; 61：1008-1013.）.在线补充资料
Nebivolol is a selective beta 1-blocker with nitric oxide-enhancing effects. MicroRNAs are small noncoding RNA molecules that downregulate gene expression. We compared the effects of nebivolol and atenolol, a first generation beta 1-selective blocker, on left ventricular hypertrophy, fibrosis, and function and microRNA expression in a rodent model of hypertension. Dahl salt-sensitive rats received either low-salt chow (control) or AIN-76A high-salt (8% NaCl) diet and randomized to vehicle (high-salt), nebivolol (20 mg/kg per day), or atenolol (50 mg/kg per day) for 8 weeks. High-salt induced left ventricular hypertrophy and fibrosis and decreased the expression of miR-27a, -29a, and -133a. Nebovolol attenuated deterioration of left ventricular systolic function, remodeling, and fibrosis more than atenolol, despite similar effects on heart rate and blood pressure. Nebivolol, but not atenolol, prevented the decrease in miR-27a and -29a induced by high-salt. Nebivolol and atenolol equally attenuated the decrease in miR-133a. In vitro overexpression of miR-27a, -29a, and -133a inhibited cardiomyocyte hypertrophy and reduced collagen expression. Both miR-27a and -29a target Sp1, and miR-133a targets Cdc42. Pharmacological inhibition of Sp1 and Cdc42 decreased myocardial fibrosis and hypertrophy. Our data support a differential microRNAs expression profile in salt-induced hypertension. Nebivolol substantially attenuated cardiac remodeling, hypertrophy, and fibrosis more than atenolol. These effects are related to attenuation of the hypertension-induced decrease in miR-27a and -29a (with a subsequent decrease in Sp1 expression) and miR-133a (with a subsequent decrease in Cdc42). (Hypertension. 2013; 61: 1008-1013.) . Online Data Supplement