Cardiac Malformations Are Associated with Altered Expression of Vascular Endothelial Growth Factor and Endothelial Nitric Oxide Synthase Genes in Embryos of Diabetic Mice
doi: 10.3181/0806-rm-186
pmid: 18824721
Cardiac Malformations Are Associated with Altered Expression of Vascular Endothelial Growth Factor and Endothelial Nitric Oxide Synthase Genes in Embryos of Diabetic Mice
The aim of this study was to investigate the role of nitric oxide (NO), and the expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) genes in developing hearts at embryonic day 13.5 of embryos from diabetic mice. The protein and mRNA expression levels of eNOS and VEGF were significantly altered in the developing hearts of embryos from diabetic mice. The NO level was significantly decreased, whereas the VEGF concentration was significantly increased in the developing hearts of the embryos from diabetic mice. In vitro study showed a significant reduction in eNOS expression and cell proliferation in cardiac myoblast cells exposed to high glucose concentrations. Further, high glucose induced apoptosis in myoblast cells. Ultrastructural changes characteristics of apoptosis, including cell blebbing, aggregation of ribosomes and vacuoles in the cytoplasm were also evident in myoblast cells exposed to high glucose. It is suggested that hyperglycemia alters the expression of eNOS and VEGF genes that are involved in the regulation of cell growth and vasculogenesis, thereby contributing to the cardiac malformations seen in embryos from diabetic mice.
- National University of Singapore Libraries Singapore
- National University of Singapore Singapore
- National University Health System Singapore
CONGENITAL HEART-DEFECTS, Heart Defects, Congenital, Vascular Endothelial Growth Factor A, mice, MOUSE HEART, INFANTS, 610, Embryonic Development, Apoptosis, Research & Experimental Medicine, GLUCOSE, Diabetes Mellitus, Experimental, 618, Mice, 616, developing heart, Animals, RNA, Messenger, OXIDATIVE STRESS, maternal diabetes, Cells, Cultured, Cell Proliferation, Science & Technology, ENOS, Research & Experimental, MOTHERS, Myocardium, Heart, VEGF, ENDOCARDIAL CUSHION FORMATION, Rats, OUTFLOW TRACT, RAT EMBRYOS, Glucose, Developing heart, eNOS, Maternal diabetes, Medicine, Female, Nitric Oxide Synthase, Life Sciences & Biomedicine, H9C2 cell line, EARLY-PREGNANCY, Myoblasts, Cardiac
CONGENITAL HEART-DEFECTS, Heart Defects, Congenital, Vascular Endothelial Growth Factor A, mice, MOUSE HEART, INFANTS, 610, Embryonic Development, Apoptosis, Research & Experimental Medicine, GLUCOSE, Diabetes Mellitus, Experimental, 618, Mice, 616, developing heart, Animals, RNA, Messenger, OXIDATIVE STRESS, maternal diabetes, Cells, Cultured, Cell Proliferation, Science & Technology, ENOS, Research & Experimental, MOTHERS, Myocardium, Heart, VEGF, ENDOCARDIAL CUSHION FORMATION, Rats, OUTFLOW TRACT, RAT EMBRYOS, Glucose, Developing heart, eNOS, Maternal diabetes, Medicine, Female, Nitric Oxide Synthase, Life Sciences & Biomedicine, H9C2 cell line, EARLY-PREGNANCY, Myoblasts, Cardiac
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