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 (V 1 ), at 12 months (V 2 ), and at 24 months of GH treatment (V 3 ). IGF-1 levels rose under GH replacement (mean±SD): V 1 , 151.6±91.9 μg/mL; V 2 , 270.2±114.8 μg/mL; and V 3 , 266.2±109. 8 (V 1 versus V 2 ; P < 0.001: V 2 versus V 3 ; P=0.76). MMP-9 exhibited the most pronounced and sustained decline from 1248.0±651.1 ng/mL at V 1 , 949.2±457.7 ng/mL at V 2 , and 760.8±386.1 ng/mL at V 3 (P < 0.001 at all time points). A similar pattern was detected for VEGF levels: 358.5±209.0 pg/mL at V 1 , 310.6±225.7 pg/mL at V 2 (P < 0.001), and 283.7±202.7 pg/mL at V 3 (V 2 versus V 3 ; P=0.005). MMP-2 demonstrated a significant decline initially from V 1 to V 2 (1134.4±217.8 ng/ mL versus 1074.5±203.0 ng/mL, respectively; P=0.031), reaching a plateau at V 3 (1072.3±220.2 ng/mL) (V 2 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.
Randeva, H. S., Lewandowski, K. C., Komorowski, J., Murray, R. D., O’Callaghan, C. J., Hillhouse, E. W., … Shalet, S. M. (2004). Growth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals. Circulation, 109(20), 2405–2410. https://doi.org/10.1161/01.CIR.0000129763.51060.77