title: Emerging role of PKA/eNOS pathway in therapeutic angiogenesis for ischaemic tissue diseases.
abstract: Although an abundant amount of research has been devoted to the study of angiogenesis, its precise mechanisms are incompletely understood. Numerous clinical trials focused on therapeutic angiogenesis for the treatment of tissue ischaemia have not been as successful as those of preclinical studies. Thus, additional studies are needed to better understand critical molecular mechanisms regulating ischaemic neovascularization to identify novel therapeutic agents. Nitric oxide (NO) plays a central role in ischaemic neovascularization through the generation of cyclic guanosine monophosphate (cGMP) and the activation of several other signalling responses. Accumulated evidence suggests that endothelial protein kinase A/endothelial NO synthase (PKA/eNOS) signalling may play an important role in ischaemic disorders by promoting neovascularization. This review highlights recent advances in the role of the PKA/eNOS and NO-cGMP-kinase cascade pathway in ischaemic neovascularization. We also discuss molecular relationships of PKA/eNOS with other angiogenic pathways and explore the possibility of activation of the NO/nitrite endocrine system as potential therapeutic targets for ischaemic angiogenesis.
authors.affiliation: Department of Pathology,  LSU Health Sciences Center-Shreveport, LA,  USA.
authors.forename: Shyamal C
authors.initials: SC
authors.lastname: Bir
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
authors.forename: Jincai
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP