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Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways. Cardiovasc Diabetol 2009 Jul 31;8:43

Date

08/04/2009

Pubmed ID

19646268

Pubmed Central ID

PMC2731081

DOI

10.1186/1475-2840-8-43

Scopus ID

2-s2.0-69549124202   28 Citations

Abstract

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.

CONCLUSION: 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.

Author List

Reinking BE, Wedemeyer EW, Weiss RM, Segar JL, Scholz TD

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Apoptosis
Cardiomyopathy, Dilated
Cardiomyopathy, Hypertrophic
Caspases
Diabetes Mellitus, Experimental
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases
Female
Hypertrophy, Left Ventricular
Insulin
JNK Mitogen-Activated Protein Kinases
MAP Kinase Signaling System
Phosphoproteins
Pregnancy
Pregnancy in Diabetics
Prenatal Exposure Delayed Effects
Rats
Rats, Sprague-Dawley
Remission, Spontaneous
Ventricular Remodeling
jenkins-FCD Prod-400 0f9a74600e4e79798f8fa6f545ea115f3dd948b2