Down regulation of IGF-I and IGF-IR gene expression in right atria tissue of ventricular septal defect infants with right atria hypoxemia.
BACKGROUND
Our previous studies showed serum insulin-like growth factor-I (IGF-I) concentrations significantly decreased in infants with congenital ventricular septal defect (VSD) and that they were associated with increased concentrations of growth hormone. In order to confirm the relationship between IGF-I axis and VSD, we further compared the IGF-I and insulin-like growth factor-I receptor(IGF-IR) gene expressions in the cardiac tissue of VSD infants.


METHODS
Right atrium biopsies of 27 infants were studied. Five infants not having VSD were classified as controls (Group I). Twenty VSD patients were then divided into 2 groups according to their shunting magnitude index (level of pulmonary vascular resistance compared with systemic vascular resistance, Qp/Qs). VSD patients with minor shunts (Qp/Qs<1.7) were classified as Group II; VSD patients with larger shunts (Qp/Qs> or =2) as Group III. Besides, seven tetralogy of fallot (TOF) with shunt (Qp/Qs>4) infants were classified as the Group IV. A non-radioactive DIG-RNA probe detection system, western blotting and immunohistochemistry were used to detect the gene expression levels and protein products of IGF-I and IGF-IR in the right atrium samples of VSD infants.


RESULTS
The relative protein levels of IGF-I were 0.96+/-0.05, 0.43+/-0.03, 0.15+/-0.04, 0.12+/-0.03 and IGF-IR were 0.80+/-0.08, 0.57+/-0.03, 0.38+/-0.02, 0.24+/-0.04 in the right atrium of 4 group patients. The relative mRNA levels of IGF-I were 0.95+/-0.01, 0.41+/-0.03, 0.29+/-0.05, 0.15+/-0.01 and IGF-IR were 0.85+/-0.05, 0.56+/-0.03, 0.17+/-0.01, 0.18+/-0.01, respectively. There was a significantly greater but more gradual decrease in protein levels and in mRNA levels of IGF-I and IGF-IR in Group II (p<0.05), Group III and IV (p<0.01) than in Group I. The results of immunohistochemistry also demonstrated a similar decrease in VSD patients. In addition, the decrease of mRNA and protein levels in IGF-I/IGF-IR of VSD patients show related to the saturation of oxygen in the right atrium and the ratio of systolic right ventricular pressure to left ventricular pressure.


CONCLUSIONS
We further confirmed the down regulation of IGF-I/IGF-IR in cardiac tissue of VSD infants and the decrease to be associated with shunt magnitude and the severity of hypoxemia in the cardiac chamber of VSD.
Chang
Mu-Hsin
MH
Division of Cardiology, Armed Force Taichung General Hospital, Taichung, Taiwan.
Kuo
Wei-Wen
WW
Li
Ping-Chun
PC
Lin
Ding-Yu
DY
Lee
Shin-Da
SD
Tsai
Fuu-Jen
FJ
Jong
Gwo-Ping
GP
Lin
Yueh-Min
YM
Huang
Chih-Yang
CY
Wu
Wen-Jun
WJ
D015153:Blotting, Western; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006325:Heart Atria / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D006345:Heart Septal Defects, Ventricular / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism*; D007150:Immunohistochemistry; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1