Myocardial fibrosis and TGFB expression in hyperhomocysteinemic rats.

Abstract

Hyperhomocysteinemia, characterized by an elevated plasma homocysteine concentration, leads to several clinical manifestations and particularly cardiovascular diseases. Experimental models of hyperhomocysteinemia revealed several tissue injuries including heart fibrosis and ventricular hypertrophy. In order to analyze the molecular mechanisms link to these morphological alterations, a mild hyperhomocysteinemia was induced in rats via a chronic methionine administration. Effects of methionine administration were examined by histological analysis with Sirius red staining, histomorphometric analysis, zymography, and immunoblotting. Hyperhomocysteinemia due to methionine administration produces an interstitial myocardial fibrosis and a ventricular cardiomyocyte hypertrophy, which were associated with increased expression of transforming growth factor-beta1 (TGFβ1), tissue inhibitors of metalloproteinase (TIMP) 2, and JNK activation. However, the matrix metalloproteinase 2 activity was decreased in the hearts of hyperhomocysteinemic rats. Moreover, the TIMP1 protein expression was decreased, and the TIMP1-MMP1 balance was shifted. Remodeling in cardiac tissue observed in rat model of mild hyperhomocysteinemia is associated with a dysregulation in extracellular matrix degradation which results, at least in part, from enhancement of TGFβ1 level.

• Authors: Lamia Raaf, Christophe Noll, Mohamed El Hadi Cherifi, Jane-Lise Samuel, Claude Delcayre, Jean-Maurice Delabar, Yasmina Benazzoug, Nathalie Janel
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 347 Issue 1-2 Pg. 63-70 (Jan 2011) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 20938722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tgfb1 protein, rat
• Tissue Inhibitor of Metalloproteinase-1
• Transforming Growth Factor beta1
• Homocysteine
• Collagen
• JNK Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 3
• Matrix Metalloproteinase 1

Topics

• Animals
• Collagen (metabolism)
• Enzyme Activation (drug effects)
• Extracellular Matrix (drug effects, metabolism)
• Fibrosis
• Homocysteine (blood, pharmacology)
• Hyperhomocysteinemia (blood, enzymology, metabolism, pathology)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Male
• Matrix Metalloproteinase 1 (metabolism)
• Matrix Metalloproteinase 3 (metabolism)
• Myocardium (enzymology, metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Rats
• Rats, Wistar
• Time Factors
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Transforming Growth Factor beta1 (metabolism)