Growth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals

Abstract

Background-Matrix metalloproteinases (MMP) are implicated in cardiovascular disease. Growth hormone (GH) deficiency is associated with increased cardiovascular mortality. We assessed whether GH replacement, in GH-deficient adults, has any effect on plasma levels of MMP-2 and MMP-9 and on vascular endothelial growth factor (VEGF), known to activate MMPs. Methods and Results-The study comprised 66 GH-deficient adults, 37.8±14.7 years of age (37 female). Plasma MMP-2 and MMP-9, VEGF, and insulin-like growth factor-1 (IGF-1) were measured at baseline (V1), at 12 months (V2), and at 24 months of GH treatment (V3). IGF-1 levels rose under GH replacement (mean±SD): V1, 151.6±91.9 μg/mL; V 2, 270.2±114.8 μg/mL; and V3, 266.2±109. 8 (V1 versus V2; P<0.001: V2 versus V 3; P=0.76). MMP-9 exhibited the most pronounced and sustained decline from 1248.0±651.1 ng/mL at V1, 949.2±457.7 ng/mL at V2, and 760.8±386.1 ng/mL at V3 (P<0.001 at all time points). A similar pattern was detected for VEGF levels: 358.5±209.0 pg/mL at V1, 310.6±225.7 pg/mL at V 2 (P<0.001), and 283.7±202.7 pg/mL at V3 (V 2 versus V3; P=0.005). MMP-2 demonstrated a significant decline initially from V1 to V2 (1134.4±217.8 ng/ mL versus 1074.5±203.0 ng/mL, respectively; P=0.031), reaching a plateau at V3 (1072.3±220.2 ng/mL) (V2 versus V 3; P=0.93). A negative relation existed between MMP-9 versus IGF-1 and MMP-2 versus IGF-1 (P<0.001 and P=0.007, respectively) as well as between VEGF and IGF-1 (P<0.001). Conclusions-These changes in MMPs and VEGF may contribute to the anticipated reduction in vascular mortality in hypopituitary adults receiving GH replacement.