title: Alcohol-free red wine inhibits isoproterenol-induced cardiac remodeling in rats by the regulation of Akt1 and protein kinase C alpha/beta II.
abstract: There is increasing evidence that moderate consumption of red wine containing high amount of polyphenols and anthocyanins is associated with decreased incidence of cardiovascular morbidity and mortality. Therefore, we hypothesized that cardiac hypertrophy and fibrosis as well as Akt (protein kinase B, PKB) and protein kinase C (PKC) cascades can be beneficially influenced by an alcohol-free red wine (AFRW) extract rich in 14 types of polyphenols and 4 types of anthocyanins during cardiac remodeling. To test this assumption, rats were treated with isoproterenol (ISO) to induce postinfarction remodeling and were given tap water or AFRW ad libitum for 8 weeks. Control rats received vehicle instead of ISO. Heart mass/body mass and ventricle mass/body mass ratios, diameter of cardiomyocytes, phosphorylation of PKC alpha/beta II and protein kinase B/Akt, and deposition of collagen type III were determined from the hearts of all four groups of rats. All measured gravimetric parameters, myocyte diameters and the amount of collagen type III decreased, and the phosphorylation of PKC alpha/beta II was reduced in the ISO+AFRW group compared to the ISO group. AFRW induced activation of Akt, one of the best characterized cytoprotective pathways even without ISO treatment, and this activation was further increased in the ISO+AFRW group. These data suggest that AFRW treatment has a protective effect on hearts undergoing postinfarction remodeling by repressing hypertrophy-associated increased phosphorylation of PKC alpha/beta II and by activating Akt, providing a molecular mechanism for the cardioprotective effect of red wine polyphenols.
authors.affiliation: Division of Cardiology, First Department of Medicine, Medical School of Pecs, University of Pecs, Pecs, Hungary.
authors.forename: Anita
authors.initials: A
authors.lastname: Palfi
authors.forename: Eva
authors.initials: E
authors.lastname: Bartha
authors.forename: Laszlo
authors.initials: L
authors.lastname: Copf
authors.forename: Laszlo
authors.initials: L
authors.lastname: Mark
authors.forename: Ferenc
authors.initials: F
authors.lastname: Gallyas
authors.forename: Balazs
authors.initials: B
authors.lastname: Veres
authors.forename: Endre
authors.initials: E
authors.lastname: Kalman
authors.forename: Laszlo
authors.initials: L
authors.lastname: Pajor
authors.forename: Kalman
authors.initials: K
authors.lastname: Toth
authors.forename: Robert
authors.initials: R
authors.lastname: Ohmacht
authors.forename: Balazs
authors.initials: B
authors.lastname: Sumegi
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects*; D014920:Wine
chemical_list: D002316:Cardiotonic Agents; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D007545:Isoproterenol