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Coronary Artery Spasm Related to Thiol Oxidation and Senescence Marker Protein-30 in Aging.
MedLine Citation:
PMID:  23320823     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Senescence marker protein-30 (SMP30) decreases with aging, SMP30 knock-out (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 mechanisms. Results: We measured vascular responses to acetylcholine (ACh), 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, a thiol-reducing agent (DTT). However, L-NAME, nitric oxide 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, 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 thiols level 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 eNOS 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     Date:  2013-1-16
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  -     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
FUKUSHIMA MEDICAL UNIVERISITY, Cardiology & Hematology, FUKUSHIMA, Fukushima, Japan; smyyamada0124@yahoo.co.jp.
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