Cited2 participates in cardiomyocyte apoptosis and maternal diabetes-induced congenital heart abnormality.
Gestational diabetes mellitus is a risk factor for abnormal heart development, but the molecular basis remains obscure. To further analyze this, the hyperglycemia rat and cell model were established in this study. The results showed that hyperglycemic rats gained significantly less weight during gestation than controls. The number of embryos per litter was significantly reduced in diabetic mothers compared to controls. Ventricular wall thickness was often decreased in the diabetic offspring and cardiomyocyte apoptosis participated in ventricular wall thinness. Our results also indicated that Cited2 expression decreased in the heart tissues of diabetic-exposed embryos comparing with the control. The vitro results showed that down-regulation of Cited2 was associated with high glucose-induced apoptosis in cardiomyocytes in vitro. Over-expression of Cited2 gene restrained the cardiomyocyte apoptosis induced by high glucose. Furthermore, Cited2 S192G mutation partly inhibited the capacity of Cited2 to suppress apoptosis induced by high glucose in cardiomyocytes. This showed the critical role of Cited2 in high glucose-induced cardiomyocytes apoptosis. Data from this study found the association of Cited2 down regulation with cardiomyocytes apoptosis and maternal diabetes-induced ventricular wall thinness genesis.
Department of Genetics, National Research Institute for Family Planning, Beijing, China.
Dongmei
D
Su
Department of Cardiology, Peking University People's Hospital, Beijing, China.
Jun-Xian
JX
Song
Linyi Academy of Technology Cooperation and Application, Linyi, Shandong Province, China.
Qianqian
Q
Gao
Department of Genetics, National Research Institute for Family Planning, Beijing, China.
Lina
L
Guan
Department of Genetics, National Research Institute for Family Planning, Beijing, China.
Qian
Q
Li
Department of Genetics, National Research Institute for Family Planning, Beijing, China.
Cuige
C
Shi
Department of Genetics, National Research Institute for Family Planning, Beijing, China. Electronic address: jswkysgc@126.com.
Xu
X
Ma
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D016640:Diabetes, Gestational / Q000378:metabolism*; D005260:Female; D006330:Heart Defects, Congenital / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C486381:CITED2 protein, human; C517260:CITED2 protein, rat; D050505:Mutant Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors
Cardiomyocyte apoptosis; Cited2; Heart; High glucose; Maternal diabetes