Epigallocatechin-3-gallate attenuates cardiac hypertrophy in hypertensive rats in part by modulation of mitogen-activated protein kinase signals.

Abstract

1. It has been demonstrated that epigallocatechin-3-gallate (EGCG) inhibits cardiac hypertrophy through its antihypertensive and anti-oxidant effects. However, the underlying molecular mechanism is not clear. 2. In the present study, we tested the hypothesis that EGCG attenuates transaortic abdominal aortic constriction (TAC)-induced ventricular hypertrophy by regulating mitogen-activated protein kinase (MAPK) signal pathways in hypertensive rats. Four groups of rats were used: (i) a sham-operated control group; (ii) an EGCG-treated (50 mg/kg per day, i.p., for 21 days) sham-operated group; (iii) a TAC group; and (iv) an EGCG-treated TAC group. Histological analysis of whole hearts and biochemical analyses of left ventricular (LV) tissue were used to investigate the effects of EGCG. 3. The results showed that the LV myocyte diameter and the expression of atrial natriuretic peptide, brain natriuretic peptide and β-myocardial heavy chain were significantly decreased in the EGCG-treated (50 mg/kg per day, i.p.) TAC group. Levels of reactive oxygen species and malondialdehyde in the lV were significantly reduced by EGCG in the TAC group. Total superoxide dismutase, catalase and glutathione peroxidase activities were decreased in the TAC group, and this decrease was significantly restored by EGCG treatment. Phosphorylation of extracellular signal-regulated kinase 2, p38 and c-Jun N-terminal kinase 1 was significantly reversed in the LV of EGCG-treated TAC rats (40%, 53% and 52% vs TAC, respectively), accompanied by significant inhibition of nuclear factor-κB and activator protein-1. Transaortic abdominal aortic constriction significantly upregulated LV expression of matrix metalloproteinase-9 from 32 ± 6 to 100 ± 12% and this increase was inhibited by EGCG treatment (from 100 ± 12 to 50 ± 15%). In addition, TAC decreased mitochondrial DNA copy number and the activity of respiratory chain complexes I (from 100 ± 7 to 68 ± 5%), III (from 100 ± 4 to 2 ± 5%) and IV (from 766 ± 2 to 100 ± 5%); this decrease was reversed by EGCG treatment to levels seen in sham-operated rats.

• Authors: Dan-Dan Chen, Yu-Gang Dong, Dan Liu, Jian-Gui He
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 36 Issue 9 Pg. 925-32 (Sep 2009) ISSN: 1440-1681 [Electronic] Australia
• PMID: 19298531 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• DNA, Mitochondrial
• Electron Transport Chain Complex Proteins
• MYH7 protein, rat
• NF-kappa B
• Reactive Oxygen Species
• Transcription Factor AP-1
• Natriuretic Peptide, Brain
• Malondialdehyde
• Atrial Natriuretic Factor
• Catechin
• epigallocatechin gallate
• Catalase
• Glutathione Peroxidase
• Superoxide Dismutase
• Mapk1 protein, rat
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 8
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 2
• Mmp2 protein, rat
• Matrix Metalloproteinase 9
• Mmp9 protein, rat
• Myosin Heavy Chains

Topics

• Animals
• Antioxidants (pharmacology)
• Atrial Natriuretic Factor (metabolism)
• Catalase (metabolism)
• Catechin (analogs & derivatives, pharmacology)
• DNA, Mitochondrial (metabolism)
• Disease Models, Animal
• Electron Transport Chain Complex Proteins (metabolism)
• Enzyme Activation
• Glutathione Peroxidase (metabolism)
• Hemodynamics (drug effects)
• Hypertension (complications, drug therapy, enzymology, physiopathology)
• Hypertrophy, Left Ventricular (enzymology, etiology, pathology, physiopathology, prevention & control)
• MAP Kinase Signaling System (drug effects)
• Male
• Malondialdehyde (metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mitochondria, Heart (drug effects, enzymology)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 8 (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Myocardium (enzymology, pathology)
• Myosin Heavy Chains (metabolism)
• NF-kappa B (metabolism)
• Natriuretic Peptide, Brain (metabolism)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (metabolism)
• Transcription Factor AP-1 (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)