This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Paisley, A. N. Articles by Randeva, H. S. Search for Related Content PubMed PubMed Citation Articles by Paisley, A. N. Articles by Randeva, H. S. Related Collections Neuroendocrinology and Pituitary Cardiovascular Endocrinology

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.