Cardiac Malformations Are Associated with Altered Expression of Vascular Endothelial Growth Factor and Endothelial Nitric Oxide Synthase Genes in Embryos of Diabetic Mice
Cardiac Malformations Are Associated with Altered Expression of Vascular Endothelial Growth Factor and Endothelial Nitric Oxide Synthase Genes in Embryos of Diabetic Mice
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DOI：
10.3181/0806-rm-186
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发表时间：
2008-11-01
影响因子：
3.2
通讯作者：
Tay, Samuel Sam-Wah
中科院分区：
文献类型：
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作者：
Kumar, Srinivasan Dinesh;Yong, Sook-Kwin;Tay, Samuel Sam-Wah
本研究旨在探讨一氧化氮（NO）和内皮型一氧化氮合酶（eNOS）、血管内皮生长因子（VEGF）基因在糖尿病小鼠胚胎13.5天心脏发育中的作用。eNOS和VEGF蛋白和mRNA的表达水平在糖尿病小鼠胚胎心脏发育过程中发生显著变化。在糖尿病小鼠胚胎发育心脏中，NO水平显著降低，VEGF浓度显著升高。体外研究显示，暴露于高葡萄糖浓度的心肌成肌细胞eNOS表达和细胞增殖显著降低。此外，高糖诱导成肌细胞凋亡。高糖作用下的成肌细胞凋亡的超微结构变化特征也很明显，包括细胞脱落、核糖体聚集和细胞质中的液泡。这表明，高血糖改变了参与细胞生长和血管发生调节的eNOS和VEGF基因的表达，从而导致糖尿病小鼠胚胎中的心脏畸形。中国生物医学工程学报（英文版），2008
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 blabbing, 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. Exp Biol Med 233:1421-1432, 2008