title: Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Endocriniology, Christie Hospital, Manchester, United Kingdom.
authors.forename: A N
authors.initials: AN
authors.lastname: Paisley
authors.forename: C J
authors.initials: CJ
authors.lastname: O'Callaghan
authors.forename: K C
authors.initials: KC
authors.lastname: Lewandowski
authors.forename: C
authors.initials: C
authors.lastname: Parkinson
authors.forename: M E
authors.initials: ME
authors.lastname: Roberts
authors.forename: W M
authors.initials: WM
authors.lastname: Drake
authors.forename: J P
authors.initials: JP
authors.lastname: Monson
authors.forename: P J
authors.initials: PJ
authors.lastname: Trainer
authors.forename: H S
authors.initials: HS
authors.lastname: Randeva
mesh_terms: D000172:Acromegaly / Q000097:blood* / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005260:Female; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D020778:Matrix Metalloproteinase 2; C406545:pegvisomant