title: Age-related oxidant stress with senescence marker protein-30 deficiency plays a pivotal role in coronary artery spasm.
abstract: OBJECTIVE
  We examined the mechanism of coronary artery spasm related to oxidant stress with aging in senescence marker protein-30 (SMP30)-deficient mice because SMP30 decreases with aging and SMP30 knockout (KO) mice show a short life with increased oxidant stress.
  
  
  METHODS
  To examine the effect of SMP30 on coronary artery vasomotor tone, we measured the endothelium-dependent [5-hydroxytryptamine (5-HT)] response of isolated, pressurized coronary arteries from SMP30 KO and wild-type (WT) mice (n=10 each).
  
  
  RESULTS
  In SMP30 KO mice, 5-HT-induced vasoconstriction occurred, which altered vasodilation with dithiothreitol, a thiol-reducing agent. In WT mice, 5-HT-induced vasodilation occurred. Administration of 5-HT from the aortic sinus induced a coronary artery spasm in SMP30 KO mice, which was prevented by the intravenous administration of Y-27632, rho-kinase inhibitor. The fluorescence level of monochlorobimane in coronary arteries, which covalently labels the reduced total thiols, decreased in SMP30 KO mice, but reverted to a level comparable with that of WT mice on treatment with Y-27632. From these results, SMP30 provides protection against coronary artery spasm.
  
  
  CONCLUSIONS
  Chronic oxidant stress associated with aging plays an important role in coronary artery spasm related to thiol oxidation and rho-kinase signaling.
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamada
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Machii
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Makiko
authors.initials: M
authors.lastname: Miyata
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Misaka
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
mesh_terms: D000375:Aging / Q000502:physiology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003329:Coronary Vasospasm / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D000577:Amides; D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D017382:Reactive Oxygen Species; C513324:Rgn protein, mouse; D017366:Serotonin Receptor Agonists; D013438:Sulfhydryl Compounds; C108830:Y 27632; D009569:Nitric Oxide; D012701:Serotonin; D006861:Hydrogen Peroxide; D054460:rho-Associated Kinases; D001205:Ascorbic Acid