EGCG inhibits proliferation of cardiac fibroblasts in rats with cardiac hypertrophy.
This study was carried out in order to investigate the effects of epigallocatechin gallate (EGCG) on myocardial fibrosis and cell proliferation in cardiac hypertrophy. Cardiac hypertrophy was established in rats by abdominal aortic constriction, and EGCG at doses of 25, 50 and 100 mg/kg was administered intragastrically for 6 weeks. The results showed that in the rats with cardiac hypertrophy, EGCG at 25 - 100 mg/kg dose-dependently reduced heart weight indices, decreased atrial natriuretic polypeptide and endothelin levels in plasma, but increased nitrite (the oxidative product of NO) levels in the serum and in the myocardium. EGCG also reduced the hydroxyproline concentration and decreased the proliferating cell nuclear antigen expression in the hypertrophic myocardium. EGCG remarkably inhibited pressure overload-induced c-myc increase in Western blot analysis. In cultured newborn rat cardiac fibroblasts, treatment with EGCG at 12.5 - 200 mg/L for 6 - 48 h decreased cell proliferation induced by serum. EGCG at 12.5 - 100 mg/L dose-dependently inhibited cell proliferation and DNA synthesis of fibroblasts induced by angiotensin II (Ang II) at 1 mumol/L. EGCG also significantly increased nitrite levels in culture medium, and up-regulated inducible nitric oxide synthase protein expression if compared with the Ang II group. The inhibitory effect of EGCG on cell proliferation induced by Ang II was partly blocked by pretreatment with N(omega)-nitro- L-arginine methyl ester hydrochloride. These results suggest that EGCG inhibits the proliferation of cardiac fibroblasts both in vivo and in vitro, thereby preventing myocardial fibrosis in cardiac hypertrophy. EGCG might exert its cardiac protective action through induction of NO production.
Sheng
Rui
R
Suzhou Institute of Chinese Materia Medica and Department of Pharmacology, Medical School of Suzhou University, Suzhou, PR China. zhenlungu.2003@163.com
Gu
Zhen-Lun
ZL
Xie
Mei-Lin
ML
Zhou
Wen-Xuan
WX
Guo
Ci-Yi
CY
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D028241:Camellia sinensis; D006332:Cardiomegaly / Q000188:drug therapy* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000473:pathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism
D000975:Antioxidants; D004268:DNA-Binding Proteins; D016232:Endothelins; D004791:Enzyme Inhibitors; C116115:MYCBP protein, human; D009573:Nitrites; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D002392:Catechin; C045651:epigallocatechin gallate; D052247:Nitric Oxide Synthase Type II; D006909:Hydroxyproline