The effects of growth hormone status on circulating levels of vascular growth factors.
BACKGROUND
Vascular growth factors are important not only in angiogenesis but also for the maintenance of normal endothelial integrity and function. Elevated levels of vascular endothelial growth factor (VEGF), angiopoietin-2, hepatocyte growth factor (HGF), endostatin and angiogenin have been associated with endothelial dysfunction and atherosclerosis. Both acromegaly and growth hormone deficiency (GHD) are associated with endothelial dysfunction and changes in blood vessel morphology.


OBJECTIVE
To investigate the effect of GH status on the circulating levels of angiogenic factors.


METHODS
We measured the levels of six endothelial growth modulators, four angiogenic growth factors and two inhibitors of angiogenesis in 35 untreated acromegalics, 36 untreated GH-deficient subjects and 101 normal control subjects. Fifteen GH-deficient subjects were also studied before and 1 year after treatment with GH.


RESULTS
Mean angiogenin concentrations were increased in acromegaly and decreased in GH-deficient subjects compared to control subjects. Endostatin levels showed a similar pattern although the elevated levels in acromegalic subjects did not achieve statistical significance. Angiogenin and endostatin levels both correlated significantly with IGF-I levels (R = 0.61, P < 0.001 and R = 0.22, P < 0.01, respectively). The relationship between angiogenin and IGF-I levels remained significant even after correction for gender, age, body mass index (BMI) and insulin resistance. There were no significant differences in the levels of HGF, VEGF, VEGF-C or angiopoietin-2 between the three groups. VEGF-D levels were elevated in both acromegalic and GH-deficient male subjects. A similar pattern was apparent in female subjects. After GH treatment, a significant reduction in VEGF-D levels and a significant rise in endostatin levels were observed in GH-deficient subjects. A nonsignificant increase in angiogenin levels was also observed.


CONCLUSIONS
These data indicate that significant perturbations in the levels of vascular growth modulators are present in both acromegaly and GHD. While changes in endostatin and angiogenin levels appear to correlate with IGF-I levels, VEGF-D levels show similar perturbations in both acromegaly and GHD. Further studies are required to determine the relationship of the perturbations to endothelial dysfunction in these conditions.
Silha
Josef V
JV
Department of Physiology and Internal Medicine, University of Manitoba, Winnipeg, Canada.
Krsek
Michal
M
Hana
Vaclav
V
Marek
Josef
J
Weiss
Vladimir
V
Jezkova
Jana
J
Rosicka
Martina
M
Jarkovska
Zuzana
Z
Murphy
Liam J
LJ
D000172:Acromegaly / Q000097:blood / Q000503:physiopathology*; D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D020533:Angiogenesis Inhibitors / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood; D043169:Endostatins / Q000097:blood; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood; D019382:Human Growth Hormone / Q000172:deficiency / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008593:Menopause / Q000502:physiology; D008875:Middle Aged; D012259:Ribonuclease, Pancreatic / Q000097:blood; D012737:Sex Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D042582:Vascular Endothelial Growth Factor C / Q000097:blood; D042643:Vascular Endothelial Growth Factor D / Q000097:blood
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D042702:Angiopoietin-2; D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D019382:Human Growth Hormone; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; C046366:angiogenin; D012259:Ribonuclease, Pancreatic