title: Preservation of ventricular performance at early stages of diabetic cardiomyopathy involves changes in myocyte size, number and intercellular coupling.
abstract: In a rat model of diabetic cardiomyopathy, we tested whether specific changes in myocyte turnover and intercellular coupling contribute to preserving ventricular performance after a short period of hyperglycemia. In 41 rats with streptozotocin-induced diabetes and 24 control animals, cardiac electromechanical properties were assessed by telemetry ECG, epicardial potential mapping, and hemodynamic measurements to document normal ventricular function. Myocardial remodeling, expression of gap-junction proteins and myocyte regeneration were evaluated by tissue morphometry, immunohistochemistry and immunoblotting. Ventricular myocyte number and volume were also determined. In diabetic hearts, after 3 weeks of hyperglycemia, left ventricular mass was lowered by 23%, while left ventricular wall thickness and chamber volume were maintained, in the absence of fibrosis and myocyte hypertrophy. In the presence of a marked DNA oxidative damage, an increased rate of DNA replication and mitotic divisions associated with generation of new myocytes were detected. The number of cells expressing the receptor for Stem Cell Factor (c-kit) and their rate of proliferation were preserved in the left ventricle while the atrial storage of these primitive cells was severely reduced by diabetes-induced oxidative stress. Despite a down-regulation of Connexin43 and over-expression of both Connexin40 and Connexin45, the junctional proteins were normally distributed in diabetic ventricular myocardium,justifying the preserved tissue excitability and conduction velocity. In conclusion, before the appearance of the diabetic cardiomyopathic phenotype,myocardial cell proliferation associated with gap junction protein remodeling may contribute to prevent marked alterations of cardiac structure and electrophysiological properties, preserving ventricular performance.
authors.affiliation: Dept of Evolutionary and Functional, Biology-Physiology Section, University of Parma, Parma, Italy. donatella.stilli@unipr.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Stilli
authors.forename: Costanza
authors.initials: C
authors.lastname: Lagrasta
authors.forename: Roberta
authors.initials: R
authors.lastname: Berni
authors.forename: Leonardo
authors.initials: L
authors.lastname: Bocchi
authors.forename: Monia
authors.initials: M
authors.lastname: Savi
authors.forename: Francesca
authors.initials: F
authors.lastname: Delucchi
authors.forename: Gallia
authors.initials: G
authors.lastname: Graiani
authors.forename: Manuela
authors.initials: M
authors.lastname: Monica
authors.forename: Roberta
authors.initials: R
authors.lastname: Maestri
authors.forename: Silvana
authors.initials: S
authors.lastname: Baruffi
authors.forename: Stefano
authors.initials: S
authors.lastname: Rossi
authors.forename: Emilio
authors.initials: E
authors.lastname: Macchi
authors.forename: Ezio
authors.initials: E
authors.lastname: Musso
authors.forename: Federico
authors.initials: F
authors.lastname: Quaini
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D009202:Cardiomyopathies / Q000473:pathology / Q000503:physiopathology*; D002450:Cell Communication / Q000502:physiology*; D049109:Cell Proliferation; D048429:Cell Size; D004249:DNA Damage / Q000502:physiology; D048909:Diabetes Complications / Q000473:pathology / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D020257:Ventricular Remodeling
chemical_list: D001786:Blood Glucose; D013311:Streptozocin