ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2003) 6 P40

The effect of pegvisomant therapy on plasma levels of matrix metalloproteinases 2, 9 and vascular endothelial growth factor in patients with acromegaly

AN Paisley1, HS Randeva2, C Parkinson4, H Alsafadi2, ME Roberts1, JP Monson3, WM Drake3 & PJ Trainer1

1Dept of Endocrinology, Christie Hospital, Manchester, UK; 2Molecular Medicine Research Centre, Dept of Biological Sciences, University of Warwick, Coventry, UK; 3Dept of Endocrinology, St Bartholomew's Hospital, London, UK; 4Dept of Diabetes and Endocrinology, Ipswich Hospital, Suffolk, UK

Vascular endothelial growth factor (VEGF) is involved in the activation of the matrix metalloproteinase system (MMP) which in turn degrades the extracellular matrix involved in development, morphogenesis and tissue remodelling. Increased activity of MMPs has been implicated in atherosclerosis and cardiovascular disease. This study assessed plasma MMP and VEGF levels in patients with active acromegaly (IGF-I >130%ULN), and on treatment with pegvisomant.

Methods: 20 patients [9 female, mean age 57+/-14.0 years (mean plus/minus SD)], were studied at baseline and on pegvisomant. Plasma levels of MMP-2, MMP-9 and VEGF were measured by ELISA assays. Ethical approval was obtained. The data were analysed using the Wilcoxon matched pair test.

Results: Pegvisomant resulted in a fall in IGF-I [baseline median value: 623 nanograms per millilitre (range 333-992), on pegvisomant: 215 nanograms per millilitre (91-545)]. Doses of pegvisomant ranged from 10mg to 60mg. Significant parallel reductions were noted in both MMP-2 [350.4 micrograms per litre (101.7-751.5) vs 206.3 micrograms per litre (70.8-394.7) p<0.001] and VEGF [236.52 nanograms per litre (74.01-1102.61) vs 194.32 nanograms per litre (81.73-796.34) p=0.022] (all median, range). There was no significant difference in MMP-9 levels [786.1 micrograms per litre (540-1089.1) vs 818.75 micrograms per litre (144.1-1175.8) p=0.78]. No correlation was found between MMP-2, -9 or VEGF levels and IGF-I.

Conclusions: This is the first study to demonstrate that treatment of acromegaly with pegvisomant significantly lowers both MMP-2 and VEGF concentrations, in a group of individuals with increased cardiovascular risk. Further studies will be required to determine the significance of these findings with relation to cardiovascular disease.

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