Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/13249
Title: Morphological and molecular analysis of the Developing heart in embryos of diabetic mice
Authors: SRINIVASAN DINESH KUMAR
Keywords: Diabetes, developing heart, genes, congenital heart defects, embryos, mice
Issue Date: 16-May-2008
Source: SRINIVASAN DINESH KUMAR (2008-05-16). Morphological and molecular analysis of the Developing heart in embryos of diabetic mice. ScholarBank@NUS Repository.
Abstract: Congenital heart defects (CHD) are frequently observed in infants of diabetic mothers, but the molecular basis of the defects remains obscure. Thus, the present study aimed to gain some insights into the molecular pathogenesis of maternal diabetes-induced CHD. The expression of some proteins and genes, the proliferation index and apoptosis were studied in the developing heart of embryos at E13.5 from streptozotocin-induced diabetic mice. Morphological analysis has shown the persistent truncus arteriosus (PTA) combined with a ventricular septal defect (VSD) in embryos of diabetic mice. Several other defects including defective endocardial cushion (EC) and aberrant myofibrillogenesis have also been found. Cardiac neural crest defects in experimental embryos were analyzed and validated by the protein expression of neural cell adhesion molecule (NCAM) and protein gene product 9.5 (PGP 9.5). The protein and mRNA expressions of bone morphogenetic protein-4 (Bmp4), Msx1, Pax3, endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were significantly altered in the hearts of embryos from diabetic mice. Western blot analysis demonstrated that eNOS expression was significantly decreased and VEGF expression was significantly increased in the developing heart of embryos from diabetic pregnancy. In addition, nitric oxide (NO) level nitrite/ nitrates and VEGF concentration in the heart tissues were significantly altered in embryos from diabetic mice when compared to controls. Further, the proliferation index was significantly decreased, whereas the apoptotic cells were significantly increased in the EC and the ventricular myocardium of the embryos from diabetic pregnancy. It is suggested that the altered expression of genes involved in the development of cardiac neural crest, could contribute to the pathogenesis of maternal diabetes-induced CHD.
URI: http://scholarbank.nus.edu.sg/handle/10635/13249
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