Document Detail


Nɛ-homocysteinyl-lysine isopeptide is associated with progression of peripheral artery disease in patients treated with folic acid.
MedLine Citation:
PMID:  22436266     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Folic acid (FA) administration can reduce plasma total homocysteine (tHcy); however, it fails to decrease cardiovascular events and progression of peripheral artery disease (PAD). Nɛ-homocysteinyl-lysine isopeptide (Nɛ-Hcy-Lys) is formed during catabolism of homocysteinylated proteins. We sought to investigate factors that determine the presence of Nɛ-Hcy-Lys in PAD patients with hyperhomocysteinemia receiving FA.
PATIENTS AND METHODS: We studied 131 consecutive PAD patients with tHcy > 15 μmol l(-1) taking FA 0.4 mg d(-1) for 12 months. Serum Nɛ-Hcy-Lys was determined by high-performance liquid chromatography (HPLC). We also measured interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), asymmetric dimethylarginine (ADMA) and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)).
RESULTS: FA administration resulted in a 70.5% decrease in tHcy (p < 0.0001). However, serum Nɛ-Hcy-Lys was detectable in 28 (21.4%) patients on FA who were more frequently current smokers and survivors of ischaemic stroke (p < 0.001). They had higher tHcy by 46.0%, PAI-1 by 51.7%, 8-iso-PGF(2α) by 59.1% and ADMA by 26.4% (all, p < 0.0001). The presence of Nɛ-Hcy-Lys was associated with lower ankle-brachial index (ABI) values (p < 0.001) and higher prevalence of cardiovascular events (p < 0.001) following therapy.
CONCLUSION: The presence of Nɛ-Hcy-Lys in one-fifth of hyperhomocysteinemic individuals with PAD despite FA treatment is associated with progression of PAD and with increased ADMA formation, oxidative stress and hypofibrinolysis.
Authors:
P Mazur; A Kozynacka; L Durajski; R Głowacki; R Pfitzner; K Fijorek; J Sadowski; A Undas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-20
Journal Detail:
Title:  European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery     Volume:  43     ISSN:  1532-2165     ISO Abbreviation:  Eur J Vasc Endovasc Surg     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-01     Completed Date:  2012-06-27     Revised Date:  2013-02-28    
Medline Journal Info:
Nlm Unique ID:  9512728     Medline TA:  Eur J Vasc Endovasc Surg     Country:  England    
Other Details:
Languages:  eng     Pagination:  588-93     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
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MeSH Terms
Descriptor/Qualifier:
Aged
Disease Progression
Female
Folic Acid / administration & dosage
Homocysteine / blood,  metabolism*
Humans
Hyperhomocysteinemia / blood,  drug therapy,  metabolism*
Male
Metabolism
Middle Aged
Oxidative Stress
Peptides / blood,  metabolism*
Peripheral Arterial Disease / blood,  metabolism,  physiopathology*
Proteins / metabolism*
Vitamin B Complex / administration & dosage*
Chemical
Reg. No./Substance:
0/Peptides; 0/Proteins; 12001-76-2/Vitamin B Complex; 454-28-4/Homocysteine; 59-30-3/Folic Acid
Comments/Corrections
Comment In:
Eur J Vasc Endovasc Surg. 2013 Feb;45(2):190-1   [PMID:  23305791 ]
Eur J Vasc Endovasc Surg. 2013 Feb;45(2):190   [PMID:  23276678 ]

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