Document Detail


Coronary artery spasm related to thiol oxidation and senescence marker protein-30 in aging.
MedLine Citation:
PMID:  23320823     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Senescence marker protein-30 (SMP30) decreases with aging, and SMP30 knockout (KO) mice show a short life with increased oxidant stress.
AIMS: We assessed the effect of oxidant stress with SMP30 deficiency in coronary artery spasm and clarify its underlying mechanisms.
RESULTS: We measured vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) of isolated coronary arteries from SMP30 KO and wild-type (WT) mice. In SMP30 KO mice, ACh-induced vasoconstriction occurred, which was changed to vasodilation by dithiothreitol (DTT), a thiol-reducing agent. However, Nω-nitro-L-arginine-methyl ester, nitric oxide (NO) synthase inhibitor, or tetrahydrobiopterin did not change the ACh response. In isolated coronary arteries of WT mice, ACh-induced vasodilation occurred. Inhibition of glutathione reductase by 1, 3-bis(2-chloroethyl)-1-nitrosourea decreased ACh-induced vasodilation (n=10, p<0.01), which was restored by DTT. To evaluate the thiol oxidation, we measured the fluorescence of monochlorobimane (MCB) in coronary arteries, which covalently labels the total. The fluorescence level to MCB decreased in SMP30 KO mice, but with DTT treatment restored to a level comparable to that of WT mice. The reduced glutathione and total thiol levels were also low in the aorta of SMP30 KO mice compared with those of WT mice. Administration of ACh into the aortic sinus in vivo of SMP30 KO mice induced coronary artery spasm.
INNOVATION: The thiol redox state is a key regulator of endothelial NO synthase activity, and thiol oxidation was associated with endothelial dysfunction in the SMP30 deficiency model.
CONCLUSION: These results suggest that chronic thiol oxidation by oxidant stress is a trigger of coronary artery spasm, resulting in impaired endothelium-dependent vasodilation.
Authors:
Shinya Yamada; Shu-ichi Saitoh; Hirofumi Machii; Hiroyuki Mizukami; Yasuto Hoshino; Tomofumi Misaka; Akihito Ishigami; Yasuchika Takeishi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-02-19
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  19     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-13     Completed Date:  2014-03-25     Revised Date:  2014-10-12    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1063-73     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Aging / genetics,  metabolism*,  pathology
Animals
Calcium-Binding Proteins / genetics*
Coronary Vessels / drug effects,  metabolism*,  pathology
Dithiothreitol / pharmacology
Endothelium, Vascular / drug effects*
Intracellular Signaling Peptides and Proteins / genetics*
Mice
Mice, Knockout
Nitric Oxide Synthase
Nitroprusside / pharmacology
Oxidative Stress / drug effects*
Spasm / genetics,  metabolism,  pathology
Vasoconstriction / drug effects
Vasodilation / drug effects
Chemical
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Rgn protein, mouse; 169D1260KM/Nitroprusside; EC 1.14.13.39/Nitric Oxide Synthase; N9YNS0M02X/Acetylcholine; T8ID5YZU6Y/Dithiothreitol
Comments/Corrections

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