title: Cyclic guanosine monophosphate signalling pathway in pulmonary arterial hypertension.
abstract: 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.
authors.affiliation: Experimental Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
authors.forename: Chien-nien
authors.initials: CN
authors.lastname: Chen
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Watson
authors.forename: Lan
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D015195:Drug Design; D065627:Familial Primary Pulmonary Hypertension; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D058990:Molecular Targeted Therapy; D009569:Nitric Oxide / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide; D011494:Protein Kinases; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase; D006152:Cyclic GMP