Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly
Paisley, A. N., O'Callaghan, C. J., Lewandowski, K. C., Parkinson, C., Roberts, M. E., Drake, W. M., Monson, J. P., Trainer, P. J. and Randeva, Harpal S.. (2006) Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 91 (11). pp. 4635-4640. ISSN 0021-972XFull text not available from this repository.
Official URL: http://dx.doi.org/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.
|Item Type:||Journal Article|
|Subjects:||R Medicine > RC Internal medicine|
|Journal or Publication Title:||JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM|
|Number of Pages:||6|
|Page Range:||pp. 4635-4640|
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