Preservation of ventricular performance at early stages of diabetic cardiomyopathy involves changes in myocyte size, number and intercellular coupling.
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.
Stilli
Donatella
D
Dept of Evolutionary and Functional, Biology-Physiology Section, University of Parma, Parma, Italy. donatella.stilli@unipr.it
Lagrasta
Costanza
C
Berni
Roberta
R
Bocchi
Leonardo
L
Savi
Monia
M
Delucchi
Francesca
F
Graiani
Gallia
G
Monica
Manuela
M
Maestri
Roberta
R
Baruffi
Silvana
S
Rossi
Stefano
S
Macchi
Emilio
E
Musso
Ezio
E
Quaini
Federico
F
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
D001786:Blood Glucose; D013311:Streptozocin