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

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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 (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.

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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

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