title: B-type natriuretic peptide attenuates cardiac hypertrophy via the transforming growth factor-ß1/smad7 pathway in vivo and in vitro.
abstract: 1. Previously, we showed that long-term treatment of rats after myocardial infarction (MI) with B-type natriuretic peptide (BNP) prevented ventricular remodelling. However, it is unclear whether long-term BNP treatment affects cardiac hypertrophy and, if so, its mechanism of action. In the present study, we investigated the effects of long-term BNP treatment on cardiac hypertrophy and the molecular mechanisms involved. 2. Cardiac hypertrophy was established in rats by ligation of the left anterior descending coronary artery. After treatment with BNP (5 or 15 microg/kg per day) for 8 weeks, indices of cardiac hypertrophy were determined. In separate in vitro experiments, cardiomyocyte hypertrophy was induced by treatment of cardiomyocytes with 10(-6) mol/L angiotensin (Ang) II for 48 h and cell surface area and [(3)H] incorporation were measured. Transforming growth factor (TGF)-beta1 and smad7 mRNA and protein expression in vivo and in vitro were detected using reverse transcription-polymerase chain reaction and western blotting. 3. Long-term BNP treatment dose-dependently attenuated cardiac hypertrophy and improved cardiac function in rats after MI. Furthermore, BNP attenuated the upregulation of TGF-beta1 and downregulation of smad7 mRNA and protein expression. The in vitro experiments further proved that BNP inhibited cardiac hypertrophy and changes in the TGF-beta1/smad7 pathway, which were completely blocked by the cyclic GMP-dependent protein kinase (PKG) inhibitor, KT5823 (cells were treated with 10(-6) mol/L KT5823 for 48 h). 4. The results of the present study demonstrate that long-term treatment of rats with BNP dose-dependently attenuates cardiac hypertrophy and that this is associated with downregulation of TGF-beta1 and upregulation of smad7 via PKG signalling. Long-term BNP treatment may be a new therapeutic strategy to prevent cardiac hypertrophy and progression to heart failure.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jian-Gui
authors.initials: JG
authors.lastname: He
authors.forename: Yi-Li
authors.initials: YL
authors.lastname: Chen
authors.forename: Bai-Li
authors.initials: BL
authors.lastname: Chen
authors.forename: Yi-Yi
authors.initials: YY
authors.lastname: Huang
authors.forename: Feng-Juan
authors.initials: FJ
authors.lastname: Yao
authors.forename: Sheng-Long
authors.initials: SL
authors.lastname: Chen
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Dong
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051906:Smad7 Protein / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D051906:Smad7 Protein; C497808:Smad7 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D020097:Natriuretic Peptide, Brain