Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways.
BACKGROUND
Maternal diabetes affects the developing fetal cardiovascular system. Newborn offspring of diabetic mothers can have a transient cardiomyopathy. We hypothesized that cardiomyopathic remodeling is associated with activation of the mitogen activated protein kinase (MAPK) signaling and apoptotic pathways.


METHODS
To evaluate the effects of moderate and severe maternal hyperglycemia, pregnant rats were made diabetic with an injection of 50 mg/kg of streptozotocin. Moderately well controlled maternal diabetes was achieved with twice daily glucose checks and insulin injections. No insulin was given to severely diabetic dams. Offspring of moderate and severe diabetic mothers (OMDM and MSDM, respectively) were studied on postnatal days 1 (NB1) and 21 (NB21). Echocardiograms were performed to evaluate left ventricular (LV) dimensions and function. Myocardial MAPK and apoptotic protein levels were measured by Western blot.


RESULTS
OMDM had increased cardiac mass at NB1 compared to controls that normalized at NB21. OSDM demonstrated microsomia with relative sparing of cardiac mass and a dilated cardiomyopathy at NB1. In both models, there was a persistent increase in the HW:BW and significant activation of MAPK and apoptotic pathways at NB21.


CONCLUSIONS
The degree of maternal hyperglycemia determines the type of cardiomyopathy seen in the offspring, while resolution of both the hypertrophic and dilated cardiomyopathies is associated with activation of MAPK signaling and apoptotic pathways.
Reinking
Benjamin E
BE
Departments of Pediatrics and Internal Medicine, University of Iowa, Iowa City, IA USA 52242-1083, USA. benjamin-reinking@uiowa.edu
Wedemeyer
Elesa W
EW
Weiss
Robert M
RM
Segar
Jeffrey L
JL
Scholz
Thomas D
TD
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002311:Cardiomyopathy, Dilated / Q000151:congenital / Q000196:embryology* / Q000209:etiology / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000151:congenital / Q000196:embryology* / Q000209:etiology / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000151:congenital / Q000196:embryology* / Q000209:etiology / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D010750:Phosphoproteins / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000188:drug therapy / Q000378:metabolism*; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012075:Remission, Spontaneous; D020257:Ventricular Remodeling / Q000502:physiology
D007328:Insulin; D010750:Phosphoproteins; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases