Reductions of Circulating Matrix Metalloproteinase 2 and Vascular Endothelial Growth Factor Levels after Treatment with Pegvisomant in Subjects with Acromegaly

• Published in: The journal of clinical endocrinology and metabolism 2006-11, Vol.91 (11), p.4635-4640
• Main Authors: Paisley, A. N., O’Callaghan, C. J., Lewandowski, K. C., Parkinson, C., Roberts, M. E., Drake, W. M., Monson, J. P., Trainer, P. J., Randeva, H. S.
• Format: Article
• Language: English
• Subjects: Acromegaly - blood; Acromegaly - drug therapy; Adult; Aged; Biological and medical sciences; Body Mass Index; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Human Growth Hormone - analogs & derivatives; Human Growth Hormone - therapeutic use; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Insulin-Like Growth Factor I - analysis; Male; Matrix Metalloproteinase 2 - blood; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Vascular Endothelial Growth Factor A - blood; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2005-2589

Background: Vascular endothelial growth factor (VEGF) is involved in activation of the matrix metalloproteinase (MMP) system; the latter is implicated in atherosclerosis and cardiovascular disease. Patients with acromegaly have reduced life expectancy primarily due to cardiac disease. Aim: This study assessed plasma MMPs and VEGF levels in patients with active acromegaly (IGF-I > 130% upper limit of normal), and on treatment with pegvisomant. Subjects and Methods: Twenty patients [nine female, mean age 56.1 ± 13.8 yr (mean ± sd)] were studied at baseline and on pegvisomant therapy and compared with data from 25 healthy volunteers (12 female; 56.6 ± 14.2 yr). Plasma MMP-2, MMP-9, and VEGF levels were measured. Results: Serum IGF-I fell from a baseline (mean ± sd) level of 620.1 ± 209.3 ng/ml to 237.5 ± 118.5 ng/ml on pegvisomant (doses 10–60 mg; P < 0.001). MMP-2 levels at baseline were significantly higher in patients compared with healthy controls (380.7 ± 204.8 vs. 207.4 ± 62.6 ng/ml; P < 0.001), but with treatment a significant reduction in MMP-2 [380.7 ± 204.8 vs. 203.0 ± 77.4 ng/ml; P < 0.001] and VEGF (283.4 ± 233.6 vs. 229.1 ± 157.4 pg/ml; P = 0.008) was noted. There was no significant difference in MMP-9 levels between patients and controls at baseline (797.5 ± 142.1 vs. 788.3 ± 218.0 ng/ml; P = 0.87) or between baseline and posttreatment levels (797.5 ± 142.1 vs. 780.0 ± 214 ng/ml; P = 0.76). Conclusions: Our novel data demonstrate that treatment of acromegaly with pegvisomant leads to reductions in MMP-2 and VEGF concentrations. Further studies are required to determine the significance of these findings with relation to cardiac disease.