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

Department of Endocrinology (A.N.P., M.E.R., P.J.T.), Christie Hospital, Manchester M20 4BX, United Kingdom; Department of Community Health and Epidemiology (C.J.O.), Queen’s University, Kingston, Ontario, Canada K7L 3N6; Department of Endocrinology and Metabolic Medicine (K.C.L.), The Medical University of Lodz, 90–419 Lodz, Poland; Department of Diabetes and Endocrinology (C.P.), The Ipswich Hospital, Ipswich IP4 5PD, United Kingdom; Department of Endocrinology (M.W.D., J.P.M.), St Bartholomew’s Hospital, London EC1A 7BE, United Kingdom; and Molecular Medicine Group (H.S.R.), Department of Biological Sciences, The University of Warwick, Coventry CV4 7AL, United Kingdom

Address all correspondence and requests for reprints to: Dr. Harpal S. Randeva, FRCP, Ph.D., Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, United Kingdom. E-mail: hrandeva{at}bio.warwick.ac.uk.

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.