Document Detail


A novel IKK inhibitor suppresses heart failure and chronic remodeling after myocardial ischemia via MMP alteration.
MedLine Citation:
PMID:  19007316     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Objective: Amplification of inflammatory response in the non-infarct area plays an important role in the pathogenesis of ventricular remodeling after myocardial ischemia. Activation of nuclear factor-kappa B (NF-kappaB) is involved in this amplification through a positive feedback loop of pro- inflammatory cytokines. We investigated the efficacy of IKK blockade with IMD-0560, a novel inhibitor of IKK, in a rat myocardial ischemia model. Methods/results: Left coronary artery occlusion (28 days) was carried out in Sprague-Dawley rats. Daily intraperitoneal injections of IMD-0560 (5 mg/kg) were done after the operation. Treatment with IMD-0560 significantly improved cardiac function as indicated by the preservation of fractional shortening and lower serum brain natriuretic peptide level. Histological analysis showed that IMD-0560 treatment suppressed thinning in the infarcted area compared with vehicle-treated hearts. Moreover, in situ zymography showed matrix metalloprotease-9 activity was inhibited in the infarct area. Conclusion: We revealed that the IKK blockade is potent for the suppression of chronic ventricular remodeling after myocardial ischemia.
Authors:
Shin Wakatsuki; Jun-ichi Suzuki; Masahito Ogawa; Mayumi Masumura; Susumu Muto; Tomoko Shimizu; Kiyoshi Takayama; Akiko Itai; Mitsuaki Isobe
Related Documents :
14966366 - Enhanced expression of angiopoietin-2 and the tie2 receptor but not angiopoietin-1 or t...
21081276 - Post-myocardial infarction left ventricular myocyte remodeling: are there gender differ...
18808386 - Heart and iron deficiency anaemia in rats with renal insufficiency: the role of hepcidin.
19027736 - Interventional effect of valsartan on expression of inducible camp early repressor and ...
9030996 - Sudden death during holter electrocardiogram monitoring in a patient with variant angina.
6200856 - Atrial trigeminy induced by a normally functioning dvi pacemaker.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Expert opinion on therapeutic targets     Volume:  12     ISSN:  1744-7631     ISO Abbreviation:  Expert Opin. Ther. Targets     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-14     Completed Date:  2009-02-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101127833     Medline TA:  Expert Opin Ther Targets     Country:  England    
Other Details:
Languages:  eng     Pagination:  1469-76     Citation Subset:  IM    
Affiliation:
Tokyo Medical and Dental University, Department of Cardiovascular Medicine, 1-5-45 Yushima, Bunkyo, Tokyo, Japan,.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Benzamides / pharmacology*
Blood Pressure
Body Weight
Heart Failure / prevention & control*
Heart Rate
I-kappa B Kinase / antagonists & inhibitors*
Male
Matrix Metalloproteinases / metabolism*
Myocardial Infarction / complications*
NF-kappa B / metabolism
Rats
Rats, Sprague-Dawley
Ventricular Remodeling / drug effects*
Chemical
Reg. No./Substance:
0/Benzamides; 0/N-(2,5-bis(trifluoromethyl)phenyl)-5-bromo-2-hydroxybenzamide; 0/NF-kappa B; EC 2.7.11.10/I-kappa B Kinase; EC 3.4.24.-/Matrix Metalloproteinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrob...
Next Document:  Plasma levels of osteopontin before and 24 h after percutaneous coronary intervention.