Role of copper and homocysteine in pressure overload heart failure

William M. Hughes, Walter E. Rodriguez, Dorothea Rosenberger, Jing Chen, Utpal Sen, Neetu Tyagi, Karni S. Moshal, Thomas Vacek, Yujian Kang, Suresh C. Tyagi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalCardiovascular Toxicology
Volume8
Issue number3
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

Fingerprint

Homocysteine
Constriction
Copper
Heart Failure
Pressure
Protein-Lysine 6-Oxidase
Tissue Inhibitor of Metalloproteinase-3
Tissue Inhibitor of Metalloproteinases
Echocardiography
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 9
Hyperhomocysteinemia
Matrix Metalloproteinase Inhibitors
Nutrition
Matrix Metalloproteinases
Electrocardiography
Dilated Cardiomyopathy
Left Ventricular Hypertrophy
Fibrosis
Cardiovascular Diseases

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine

Cite this

Hughes, W. M., Rodriguez, W. E., Rosenberger, D., Chen, J., Sen, U., Tyagi, N., ... Tyagi, S. C. (2008). Role of copper and homocysteine in pressure overload heart failure. Cardiovascular Toxicology, 8(3), 137-144. https://doi.org/10.1007/s12012-008-9021-3

Role of copper and homocysteine in pressure overload heart failure. / Hughes, William M.; Rodriguez, Walter E.; Rosenberger, Dorothea; Chen, Jing; Sen, Utpal; Tyagi, Neetu; Moshal, Karni S.; Vacek, Thomas; Kang, Yujian; Tyagi, Suresh C.

In: Cardiovascular Toxicology, Vol. 8, No. 3, 01.09.2008, p. 137-144.

Research output: Contribution to journalArticle

Hughes, WM, Rodriguez, WE, Rosenberger, D, Chen, J, Sen, U, Tyagi, N, Moshal, KS, Vacek, T, Kang, Y & Tyagi, SC 2008, 'Role of copper and homocysteine in pressure overload heart failure', Cardiovascular Toxicology, vol. 8, no. 3, pp. 137-144. https://doi.org/10.1007/s12012-008-9021-3
Hughes WM, Rodriguez WE, Rosenberger D, Chen J, Sen U, Tyagi N et al. Role of copper and homocysteine in pressure overload heart failure. Cardiovascular Toxicology. 2008 Sep 1;8(3):137-144. https://doi.org/10.1007/s12012-008-9021-3
Hughes, William M. ; Rodriguez, Walter E. ; Rosenberger, Dorothea ; Chen, Jing ; Sen, Utpal ; Tyagi, Neetu ; Moshal, Karni S. ; Vacek, Thomas ; Kang, Yujian ; Tyagi, Suresh C. / Role of copper and homocysteine in pressure overload heart failure. In: Cardiovascular Toxicology. 2008 ; Vol. 8, No. 3. pp. 137-144.
@article{6896161f991241949b93c5b35fa8c030,
title = "Role of copper and homocysteine in pressure overload heart failure",
abstract = "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.",
author = "Hughes, {William M.} and Rodriguez, {Walter E.} and Dorothea Rosenberger and Jing Chen and Utpal Sen and Neetu Tyagi and Moshal, {Karni S.} and Thomas Vacek and Yujian Kang and Tyagi, {Suresh C.}",
year = "2008",
month = "9",
day = "1",
doi = "10.1007/s12012-008-9021-3",
language = "English (US)",
volume = "8",
pages = "137--144",
journal = "Cardiovascular Toxicology",
issn = "1530-7905",
publisher = "Humana Press",
number = "3",

}

TY - JOUR

T1 - Role of copper and homocysteine in pressure overload heart failure

AU - Hughes, William M.

AU - Rodriguez, Walter E.

AU - Rosenberger, Dorothea

AU - Chen, Jing

AU - Sen, Utpal

AU - Tyagi, Neetu

AU - Moshal, Karni S.

AU - Vacek, Thomas

AU - Kang, Yujian

AU - Tyagi, Suresh C.

PY - 2008/9/1

Y1 - 2008/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=55449123493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55449123493&partnerID=8YFLogxK

U2 - 10.1007/s12012-008-9021-3

DO - 10.1007/s12012-008-9021-3

M3 - Article

VL - 8

SP - 137

EP - 144

JO - Cardiovascular Toxicology

JF - Cardiovascular Toxicology

SN - 1530-7905

IS - 3

ER -