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

Article

关键词: CARDIOVASCULAR RISK-FACTORS;    GH REPLACEMENT;    FACTOR-I;    MYOCARDIAL-INFARCTION;    PREMATURE MORTALITY;    TISSUE INHIBITORS;    FACTOR EXPRESSION;    PERIPHERAL-BLOOD;    POTENTIAL ROLE;    ADULT PATIENTS;   

DOI  :  10.1161/01.CIR.0000129763.51060.77

来源: SCIE

【 摘 要 】

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 mug/mL; V-2, 270.2 +/- 114.8 mug/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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