title: Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes.
abstract: Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function.
authors.affiliation: Heart Institute (InCor) University of São Paulo Medical School, Av. Dr. Eneas Carvalho Aguiar n° 44, 05403-000, São Paulo, SP, Brazil. Electronic address: labcelia@incor.usp.br.
authors.forename: Célia Maria Cássaro
authors.initials: CMC
authors.lastname: Strunz
authors.affiliation: Heart Institute (InCor) University of São Paulo Medical School, Av. Dr. Eneas Carvalho Aguiar n° 44, 05403-000, São Paulo, SP, Brazil. Electronic address: alessandra.roggerio@incor.usp.br.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Roggerio
authors.affiliation: Heart Institute (InCor) University of São Paulo Medical School, Av. Dr. Eneas Carvalho Aguiar n° 44, 05403-000, São Paulo, SP, Brazil. Electronic address: paulalcruz@gmail.com.
authors.forename: Paula Lázara
authors.initials: PL
authors.lastname: Cruz
authors.affiliation: Heart Institute (InCor) University of São Paulo Medical School, Av. Dr. Eneas Carvalho Aguiar n° 44, 05403-000, São Paulo, SP, Brazil. Electronic address: ana.pacanaro@incor.usp.br.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Pacanaro
authors.affiliation: Heart Institute (InCor) University of São Paulo Medical School, Av. Dr. Eneas Carvalho Aguiar n° 44, 05403-000, São Paulo, SP, Brazil. Electronic address: verasalemi@uol.com.br.
authors.forename: Vera Maria Cury
authors.initials: VMC
authors.lastname: Salemi
authors.affiliation: Heart Institute (InCor) University of São Paulo Medical School, Av. Dr. Eneas Carvalho Aguiar n° 44, 05403-000, São Paulo, SP, Brazil. Electronic address: benvenutianpluiz@incor.usp.br.
authors.forename: Luiz Alberto
authors.initials: LA
authors.lastname: Benvenuti
authors.affiliation: Heart Institute (InCor) University of São Paulo Medical School, Av. Dr. Eneas Carvalho Aguiar n° 44, 05403-000, São Paulo, SP, Brazil. Electronic address: antonio.mansur@incor.usp.br.
authors.forename: Antonio de Pádua
authors.initials: AP
authors.lastname: Mansur
authors.affiliation: Heart Institute (InCor) University of São Paulo Medical School, Av. Dr. Eneas Carvalho Aguiar n° 44, 05403-000, São Paulo, SP, Brazil. Electronic address: maria.irigoyen@incor.usp.br.
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Irigoyen
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D053673:Glypicans / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D053671:Syndecan-4 / Q000378:metabolism
chemical_list: D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; C508307:Sdc4 protein, rat; D013267:Stilbenes; D053671:Syndecan-4; D016222:Fibroblast Growth Factor 2; D000077185:Resveratrol
keywords: Diabetic rats; Diastolic dysfunction; FGF2; HSPGs; Resveratrol