Nitric oxide stimulates elastin expression in chick aortic smooth muscle cells.
Nitric oxide (NO), an endothelium-dependent relaxing factor, regulates relaxation, proliferation, and migration of smooth muscle cells (SMCs) and most likely attenuates developing vascular disease such as atherosclerosis. We investigated whether or not NO is associated with regulation of aortic elasticity. S-Nitrosoglutathione (GSNO), a NO donor, stimulated tropoelastin synthesis in cultured SMCs during both the quiescent and proliferating phases. The stimulation of tropoelastin synthesis was dose-dependent within 1-100 nM. Maximum stimulation was detected by treatment with 100 nM GSNO for 24 h. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP), an exogenous cyclic GMP analog, also upregulated tropoelastin synthesis. Tropoelastin and lysyl oxidase mRNA expression, as assessed by Northern blot analysis, was also stimulated by GSNO. Administration of KT5823, a cyclic GMP-dependent protein kinase inhibitor, inhibited the GSNO-induced tropoelastin synthesis. These results indicate that the stimulatory effects of GSNO are due to cyclic GMP dependent protein kinase (PKG) activation by NO. In conclusion, NO seems to enhance aortic elasticity via tropoelastin and lysyl oxidase upregulation.
Sugitani
H
H
Department of Clinical Chemistry, Hoshi College of Pharmacy, Tokyo, Japan.
Wachi
H
H
Tajima
S
S
Seyama
Y
Y
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D004549:Elastin / Q000096:biosynthesis*; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D009603:Nitroso Compounds / Q000494:pharmacology; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D026422:S-Nitrosoglutathione; D014333:Tropoelastin / Q000096:biosynthesis / Q000235:genetics
D009603:Nitroso Compounds; D012333:RNA, Messenger; D014333:Tropoelastin; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase; D017869:Cyclic GMP-Dependent Protein Kinases; D005978:Glutathione; D006152:Cyclic GMP