Document Detail


Role of copper and homocysteine in pressure overload heart failure.
MedLine Citation:
PMID:  18679830     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart.
Authors:
William M Hughes; Walter E Rodriguez; Dorothea Rosenberger; Jing Chen; Utpal Sen; Neetu Tyagi; Karni S Moshal; Thomas Vacek; Y James Kang; Suresh C Tyagi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cardiovascular toxicology     Volume:  8     ISSN:  1530-7905     ISO Abbreviation:  Cardiovasc. Toxicol.     Publication Date:  2008  
Date Detail:
Created Date:  2008-09-09     Completed Date:  2008-11-06     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  101135818     Medline TA:  Cardiovasc Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  137-44     Citation Subset:  IM    
Affiliation:
Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / surgery
Blood Pressure
Blotting, Western
Cardiomyopathy, Dilated / drug therapy*,  metabolism,  physiopathology
Constriction
Copper / administration & dosage*,  metabolism
Dietary Supplements*
Disease Models, Animal
Echocardiography
Electrocardiography
Endothelium, Vascular / drug effects,  metabolism,  physiopathology
Female
Fibrosis
Heart Failure / drug therapy*,  metabolism,  physiopathology
Hemodynamics / drug effects*
Homocysteine / blood,  metabolism*
Hypertrophy, Left Ventricular / drug therapy*,  metabolism,  physiopathology
Male
Matrix Metalloproteinases / metabolism
Mice
Mice, Inbred C57BL
Myocardium / enzymology,  metabolism*,  pathology
Protein-Lysine 6-Oxidase / metabolism
Tissue Inhibitor of Metalloproteinases / metabolism
Ventricular Remodeling / drug effects
Grant Support
ID/Acronym/Agency:
HL-74185/HL/NHLBI NIH HHS; HL-88012/HL/NHLBI NIH HHS; R01 HL074185-05/HL/NHLBI NIH HHS; R01 HL088012-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Tissue Inhibitor of Metalloproteinases; 454-28-4/Homocysteine; 7440-50-8/Copper; EC 1.4.3.13/Protein-Lysine 6-Oxidase; EC 3.4.24.-/Matrix Metalloproteinases
Comments/Corrections

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


Previous Document:  Genetic testing for BRCA1: effects of a randomised study of knowledge provision on interest in testi...
Next Document:  Evidence that the modulatory effect of galanin on inflammatory edema formation is mediated by the ga...