Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly

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