Growth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals.
BACKGROUND
Matrix metalloproteinases (MMP) are implicated in cardiovascular disease. Growth hormone (GH) deficiency is associated with increased cardiovascular mortality. We assessed whether GH replacement, in GH-deficient adults, has any effect on plasma levels of MMP-2 and MMP-9 and on vascular endothelial growth factor (VEGF), known to activate MMPs.


RESULTS
The study comprised 66 GH-deficient adults, 37.8+/-14.7 years of age (37 female). Plasma MMP-2 and MMP-9, VEGF, and insulin-like growth factor-1 (IGF-1) were measured at baseline (V1), at 12 months (V2), and at 24 months of GH treatment (V3). IGF-1 levels rose under GH replacement (mean+/-SD): V1, 151.6+/-91.9 microg/mL; V2, 270.2+/-114.8 microg/mL; and V3, 266.2+/-109.8 (V1 versus V2; P<0.001: V2 versus V3; P=0.76). MMP-9 exhibited the most pronounced and sustained decline from 1248.0+/-651.1 ng/mL at V1, 949.2+/-457.7 ng/mL at V2, and 760.8+/-386.1 ng/mL at V3 (P<0.001 at all time points). A similar pattern was detected for VEGF levels: 358.5+/-209.0 pg/mL at V1, 310.6+/-225.7 pg/mL at V2 (P<0.001), and 283.7+/-202.7 pg/mL at V3 (V2 versus V3; P=0.005). MMP-2 demonstrated a significant decline initially from V1 to V2 (1134.4+/-217.8 ng/mL versus 1074.5+/-203.0 ng/mL, respectively; P=0.031), reaching a plateau at V3 (1072.3+/-220.2 ng/mL) (V2 versus V3; P=0.93). A negative relation existed between MMP-9 versus IGF-1 and MMP-2 versus IGF-1 (P<0.001 and P=0.007, respectively) as well as between VEGF and IGF-1 (P<0.001).


CONCLUSIONS
These changes in MMPs and VEGF may contribute to the anticipated reduction in vascular mortality in hypopituitary adults receiving GH replacement.
Randeva
Harpal S
HS
Molecular Medicine Research Group, Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. hrandeva@bio.warwick.ac.uk
Lewandowski
Krzysztof C
KC
Komorowski
Jan
J
Murray
Robert D
RD
O'Callaghan
Chris J
CJ
Hillhouse
Edward W
EW
Stepien
Henryk
H
Shalet
Stephen M
SM
D000328:Adult; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9