IGF-II and MMP9 as surgical repair indicators of ventricular septal defects.
OBJECTIVE
The insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and human growth hormone (h-GH) have been recognized as therapeutic targets for the heart disease therapy. The bioavailability and actions of insulin-like growth factors-II (IGF-II) and matrix metalloproteinase-9 (MMP9) are important for embryonic development and cardiomyocyte differentiation as well. However, the clinical manifestations following the change in the serum IGF-II and MMP9 in infants with isolated ventricular septal defect (VSD) undergoing surgical repair have not been clearly defined.


METHODS
Serum samples were collected from 72 infants: Twenty normal infants (group I) and 51 consecutive infants with echocardiography established isolated VSD (aged from 3 months to 1 year) were investigated. Among the 51 infants with VSD, 28 with shunt fraction, Qp/Qs < or = 1.5 were free of congestive heart failure symptoms (group II); 23 with shunt fraction, Qp/Qs > or = 2.0 were in congestive heart failure (group IIIa); and 23 of these 23 infants had undergone VSD repair 6 months before their second study (group IIIb). All insulin-like growth factors-II (IGF-II) and human growth hormone (h-GH), insulin like growth factor binding protein-3 (IGFBP-3) and its specific serum protease-MMP9 concentration were analyzed using ELISA and zymography, respectively.


RESULTS
Serum IGF-II and MMP9 exhibited significant decreasing trends among the three groups and significantly lower concentrations of IGF-II, IGF-II/IGFBP-3 ratio and MMP9, were found only in the severe group whereas h-GH/IGF-II ratio became significantly higher in this group. Moreover, there were no significant differences in these parameters between the infants after surgical correction and the normal ones.


CONCLUSIONS
The improvement in IGF-II and MMP9 serum concentration was identified in infants with VSD after surgical repair. These findings also indicate a significant relationship between IGF-II, MMP9 and VSD which might be used as diagnosis and prognosis indicators for this defect. Slight reductions in IGF-II/IGFBP3 ratio and slight increase in the h-GH/IGF-II ratio indicate mild VSD. The reductions in the MMP9, IGF-II, and IGF-II/IGFBP3 ratio plus high increase in the h-GH/IGF-II ratio indicate severe VSD.
Department of Pediatrics, China Medical University Beigang Hospital, Yunlin, Taiwan.
Chen-Yen
CY
Tsai
Chao-Hung
CH
Lai
Mu-Hsin
MH
Chang
Gwo-Ping
GP
Jong
Yi-Chang
YC
Cheng
Fuu-Jen
FJ
Tsai
Chang-Hai
CH
Tsai
Wu-Hsien
WH
Kuo
Dennis Jine-Yuan
DJ
Hsieh
Chih-Yang
CY
Huang
D005260:Female; D006345:Heart Septal Defects, Ventricular / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000601:surgery*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D011379:Prognosis; D012709:Serum Albumin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000097:blood
D018972:Insulin-Like Growth Factor Binding Protein 3; D012709:Serum Albumin; D019382:Human Growth Hormone; D019344:Lactic Acid; D007335:Insulin-Like Growth Factor II; D010959:Tissue Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9