Experimental Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
Vascul Pharmacol. 2013 Mar;58(3):211-8. doi: 10.1016/j.vph.2012.09.001. Epub 2012 Sep 12.
During the last decade, it emerged that cyclic guanosine monophosphate (cGMP) is a novel drug target for the treatment of pulmonary arterial hypertension (PAH). cGMP regulates many cellular functions, ranging from contractility to growth, of relevance to the disease. Generated from guanylyl cyclases in response to natriuretic peptides or nitric oxide (NO), cGMP transduces its effects through a number of cGMP effectors, including cGMP-regulated phosphodiesterases and protein kinases. Furthermore, the cGMP concentration is modulated by cGMP-degrading phosphodiesterases. Data to date demonstrate that increasing intracellular cGMP through stimulation of GCs, inhibition of PDEs, or both is a valid therapeutic strategy in drug development for PAH. New advances in understanding of cGMP are unravelled, as well as the pathobiology of PAH. cGMP remains an attractive future PAH drug target. This review makes a more detailed examination of cGMP signalling with particular reference to PAH.
在过去的十年中，人们发现环鸟苷酸（cGMP）是肺动脉高压（PAH）治疗的新型药物靶点。cGMP 调节许多与疾病相关的细胞功能，从收缩性到生长。cGMP 是由鸟苷酸环化酶响应利钠肽或一氧化氮（NO）产生的，通过多种 cGMP 效应物（包括 cGMP 调节的磷酸二酯酶和蛋白激酶）传递其作用。此外，cGMP 浓度可通过 cGMP 降解磷酸二酯酶进行调节。迄今为止的数据表明，通过刺激 GC、抑制 PDE 或两者兼用来增加细胞内 cGMP 是 PAH 药物开发中的一种有效治疗策略。人们对 cGMP 的理解以及 PAH 的病理生物学有了新的进展。cGMP 仍然是一个有吸引力的未来 PAH 药物靶点。本综述更详细地研究了 cGMP 信号转导，特别是与 PAH 相关的信号转导。
