Document Detail

The non-anticoagulant heparin-like K5 polysaccharide derivative K5-N,OSepi attenuates myocardial ischaemia/reperfusion injury.
MedLine Citation:
PMID:  22248092     Owner:  NLM     Status:  MEDLINE    
Heparin and low molecular weight heparins have been demonstrated to reduce myocardial ischaemia/reperfusion (I/R) injury, although their use is hampered by the risk of haemorrhagic and thrombotic complications. Chemical and enzymatic modifications of K5 polysaccharide have shown the possibility of producing heparin-like compounds with low anticoagulant activity and strong anti-inflammatory effects. Using a rat model of regional myocardial I/R, we investigated the effects of an epimerized N-,O-sulphated K5 polysaccharide derivative, K5-N,OSepi, on infarct size and histological signs of myocardial injury caused by 30 min. ligature of the left anterior descending coronary artery followed by 1 or 24 h reperfusion. K5-N,OSepi (0.1-1 mg/kg given i.v. 15 min. before reperfusion) significantly reduced the extent of myocardial damage in a dose-dependent manner. Furthermore, we investigated the potential mechanism(s) of the cardioprotective effect(s) afforded by K5-N,OSepi. In left ventricular samples, I/R induced mast cell degranulation and a robust increase in lipid peroxidation, free radical-induced DNA damage and calcium overload. Markers of neutrophil infiltration and activation were also induced by I/R in rat hearts, specifically myeloperoxidase activity, intercellular-adhesion-molecule-1 expression, prostaglandin-E(2) and tumour-necrosis-factor-α production. The robust increase in oxidative stress and inflammatory markers was blunted by K5-N,OSepi, in a dose-dependent manner, with maximum at 1 mg/kg. Furthermore, K5-N,OSepi administration attenuated the increase in caspase 3 activity, Bid and Bax activation and ameliorated the decrease in expression of Bcl-2 within the ischaemic myocardium. In conclusion, we demonstrate that the cardioprotective effect of the non-anticoagulant K5 derivative K5-N,OSepi is secondary to a combination of anti-apoptotic and anti-inflammatory effects.
Massimo Collino; Collino Massimo; Alessandro Pini; Pini Alessandro; Rosanna Mastroianni; Mastroianni Rosanna; Elisa Benetti; Benetti Elisa; Cecilia Lanzi; Lanzi Cecilia; Daniele Bani; Bani Daniele; Chini Jacopo; Marco Manoni; Manoni Marco; Roberto Fantozzi; Fantozzi Roberto; Emanuela Masini; Masini Emanuela
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  16     ISSN:  1582-4934     ISO Abbreviation:  J. Cell. Mol. Med.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-23     Completed Date:  2013-01-07     Revised Date:  2014-02-10    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  2196-207     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
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MeSH Terms
Anti-Inflammatory Agents / pharmacology
Anticoagulants / pharmacology*
Apoptosis / drug effects
Bacterial Capsules / metabolism*
Calcium / analysis
Caspase 3 / analysis,  metabolism
Deoxyguanosine / analogs & derivatives,  analysis
Diagnosis, Computer-Assisted / methods
Dinoprostone / analysis,  metabolism
Heparin / pharmacology*
Inflammation / drug therapy,  pathology
Myocardial Reperfusion Injury / drug therapy*,  pathology
Myocardium / metabolism,  pathology
Rats, Wistar
Thiobarbituric Acid Reactive Substances
Tumor Necrosis Factor-alpha / analysis,  metabolism
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Anticoagulants; 0/Thiobarbituric Acid Reactive Substances; 0/Tumor Necrosis Factor-alpha; 42615-44-1/capsular polysaccharide K5; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; 9005-49-6/Heparin; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; G9481N71RO/Deoxyguanosine; K7Q1JQR04M/Dinoprostone; SY7Q814VUP/Calcium
Erratum In:
J Cell Mol Med. 2013 Dec;17(12):1652
Note: Massimo, Collino [corrected to Collino, Massimo]; Alessandro, Pini [corrected to Pini, Alessandro]; Rosanna, Mastroianni [corrected to Mastroianni, Rosanna]; Elisa, Benetti [corrected to Benetti, Elisa]; Cecilia, Lanzi [corrected to Lanzi, Cecilia]; Daniele, Bani [corrected to Bani, Daniele]; Marco, Manoni [corrected to Manoni, Marco]; Roberto, Fantozzi [corrected to Fantozzi, Roberto]; Emanuela, Masini [corrected to Masini, Emanuela]; Jacopo, Chini [removed]

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