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Cyclic GMP-dependent protein kinases and the cardiovascular system: insights from genetically modified mice.
环 GMP 依赖性蛋白激酶与心血管系统: 来自转基因小鼠的见解。

摘要

Signaling cascades initiated by nitric oxide (NO) and natriuretic peptides (NPs) play an important role in the maintenance of cardiovascular homeostasis. It is currently accepted that many effects of these endogenous signaling molecules are mediated via stimulation of guanylyl cyclases and intracellular production of the second messenger cGMP. Indeed, cGMP-elevating drugs like glyceryl trinitrate have been used for more than 100 years to treat cardiovascular diseases. However, the molecular mechanisms of NO/NP signaling downstream of cGMP are not completely understood. Recent in vitro and in vivo evidence identifies cGMP-dependent protein kinases (cGKs) as major mediators of cGMP signaling in the cardiovascular system. In particular, the analysis of conventional and conditional knockout mice indicates that cGKs are critically involved in regulating vascular remodeling and thrombosis. Thus, cGKs may represent novel drug targets for the treatment of human cardiovascular disorders.

译文

由一氧化氮 (NO) 和利钠肽 (NPs) 启动的信号级联反应在维持心血管稳态中起着重要作用。目前公认的是,这些内源性信号分子的许多作用是通过鸟苷酸环化酶的刺激和第二信使 cGMP 的细胞内生产来介导的。事实上,增强 cGMP 的药物,如三氮甘油酯,已经被用于治疗心血管疾病超过 100 年了。然而,cGMP 下游 NO/NP 信号的分子机制尚不完全清楚。最近的体外和体内证据确定 cGMP 依赖性蛋白激酶 (cGKs) 是心血管系统中 cGMP 信号传导的主要介质。特别是,对常规和条件性基因敲除小鼠的分析表明 cGKs 与调节血管重塑和血栓形成密切相关。因此,cGKs 可能代表治疗人类心血管疾病的新药物靶点。

genetically modified mice

肿瘤 转基因 动物模型
概述  :  

转基因小鼠是指染色体基因组中整合有外源基因并能表达的稳定遗传的小鼠。转基因技术则是指制备转基因动物所需的一套技术,它涉及外源基因的构建、载体和受体的筛选、基因导人技术、供转基因胚胎发育的体外培养系统和宿主动物等许多方面。   1974年,Jaenish和Mintz应用显微注射法,在世界上首次成功地获得了SV40 DNA转基因小鼠。1980年,Gordon等人首先育成带有人胸腺激酶基因的转基因小鼠,尤其是1982年Palmiter等人将大鼠的生长

Genetically   英 /dʒəˈnetɪkli/   美 /dʒə'nɛtɪklɪ/

释    义   adv. 从遗传学角度;从基因方面

例    句   These attributes are genetically programmed functions of normal cells that are intended to combat infection or repair injury. 这些属性是正常细胞的基因编程功能,此举的目的是抗击感染或修复损伤。

 

Modified   英 /ˈmɒdɪfaɪd/   美 /mɑdəˌfaɪd/

释    义   adj. 改进的,修改的;改良的

               v. 修改;缓和(modify的过去分词)

同根词   modifiable adj. 可修饰的;可更改的

               modification n. 修改,修正;改变

               modify vi. 修改

               modify vt. 修改,修饰;更改

例    句   Its systems move virtual models of prototype machinery and products around manufacturing plants to determine how existing equipment would have to be moved or modified. 该系统将原型机械与产品的虚拟模型在制造厂内到处移动,以决定现有的设备需要怎样的移动或改进。

 

Mice   英 /maɪs/   美 /maɪs/

释    义   n. 老鼠(mouse的复数)

例    句   So Tsai decided to see if they would have any effect on her mice with damaged brain cells.所以蔡决定看看它们是否会对她的脑细胞受损的老鼠有任何影响。

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