title: Parenchymal and Stromal Cells Contribute to Pro-Inflammatory Myocardial Environment at Early Stages of Diabetes: Protective Role of Resveratrol.
abstract: Background:Little information is currently available concerning the relative contribution of cardiac parenchymal and stromal cells in the activation of the pro-inflammatory signal cascade, at the initial stages of diabetes. Similarly, the effects of early resveratrol (RSV) treatment on the negative impact of diabetes on the different myocardial cell compartments remain to be defined.Methods:In vitro challenge of neonatal cardiomyocytes and fibroblasts to high glucose and in vivo/ex vivo experiments on a rat model of Streptozotocin-induced diabetes were used to specifically address these issues.Results:In vitro data indicated that, besides cardiomyocytes, neonatal fibroblasts contribute to generating initial changes in the myocardial environment, in terms of pro-inflammatory cytokine expression. These findings were mostly confirmed at the myocardial tissue level in diabetic rats, after three weeks of hyperglycemia. Specifically, monocyte chemoattractant protein-1 and Fractalkine were up-regulated and initial abnormalities in cardiomyocyte contractility occurred. At later stages of diabetes, a selective enhancement of pro-inflammatory macrophage M1 phenotype and a parallel reduction of anti-inflammatory macrophage M2 phenotype were associated with a marked disorganization of cardiomyocyte ultrastructural properties. RSV treatment inhibited pro-inflammatory cytokine production, leading to a recovery of cardiomyocyte contractile efficiency and a reduced inflammatory cell recruitment.Conclusion:Early RSV administration could inhibit the pro-inflammatory diabetic milieu sustained by different cardiac cell types.
authors.affiliation: The Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, 43125 Parma, Italy. monia.savi@unipr.it.|Department of Life Sciences, University of Parma, 43124 Parma, Italy. monia.savi@unipr.it.
authors.forename: Monia
authors.initials: M
authors.lastname: Savi
authors.affiliation: Department of Life Sciences, University of Parma, 43124 Parma, Italy. leonardo.bocchi@unipr.it.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Bocchi
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, 43126 Parma, Italy. roberto.sala@unipr.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sala
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, 43126 Parma, Italy. caterina.frati@unipr.it.|Department of Clinical and Experimental Medicine, University of Parma, 43126 Parma, Italy. caterina.frati@unipr.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Frati
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, 43126 Parma, Italy. costanzaannamaria.lagrasta@unipr.it.
authors.forename: Costanza
authors.initials: C
authors.lastname: Lagrasta
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, 43126 Parma, Italy. denise.madeddu@unipr.it.|Department of Clinical and Experimental Medicine, University of Parma, 43126 Parma, Italy. denise.madeddu@unipr.it.
authors.forename: Denise
authors.initials: D
authors.lastname: Madeddu
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, 43126 Parma, Italy. angela.falco@unipr.it.|Department of Clinical and Experimental Medicine, University of Parma, 43126 Parma, Italy. angela.falco@unipr.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Falco
authors.affiliation: Department of Life Sciences, University of Parma, 43124 Parma, Italy. serena.pollino@studenti.unipr.it.
authors.forename: Serena
authors.initials: S
authors.lastname: Pollino
authors.affiliation: The Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, 43125 Parma, Italy. letizia.bresciani@unipr.it.
authors.forename: Letizia
authors.initials: L
authors.lastname: Bresciani
authors.affiliation: Humanitas Clinical and Research Centre, Rozzano, 20089 Milan, Italy. Michele.Miragoli@humanitasresearch.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Miragoli
authors.affiliation: Department of Life Sciences, University of Parma, 43124 Parma, Italy. massimiliano.zaniboni@unipr.it.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Zaniboni
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, 43126 Parma, Italy. federico.quaini@unipr.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Quaini
authors.affiliation: The Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, 43125 Parma, Italy. daniele.delrio@unipr.it.|NNEdPro Global Centre for Nutrition and Health, St John's Innovation Centre, Cowley Road, Cambridge CB4 0WS, UK. daniele.delrio@unipr.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Del Rio
authors.affiliation: Department of Life Sciences, University of Parma, 43124 Parma, Italy. donatella.stilli@unipr.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Stilli
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages; D008297:Male; D009206:Myocardium / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013267:Stilbenes; D000077185:Resveratrol; D002118:Calcium
keywords: cardiac cell compartments; cardiomyocyte mechanics; cytokines; diabetes; intracellular calcium dynamics; polyphenols