Growth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals.
dc.contributor.author | Randeva, Harpal S | |
dc.contributor.author | Lewandowski, Krzysztof C | |
dc.contributor.author | Komorowski, Jan | |
dc.contributor.author | Murray, Robert D | |
dc.contributor.author | O'Callaghan, Chris J | |
dc.contributor.author | Hillhouse, Edward W | |
dc.contributor.author | Stepien, Henryk | |
dc.contributor.author | Shalet, Stephen M | |
dc.date.accessioned | 2009-08-26T16:22:46Z | |
dc.date.available | 2009-08-26T16:22:46Z | |
dc.date.issued | 2004-05-25 | |
dc.identifier.citation | Growth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals. 2004, 109 (20):2405-10 Circulation | en |
dc.identifier.issn | 1524-4539 | |
dc.identifier.pmid | 15123527 | |
dc.identifier.doi | 10.1161/01.CIR.0000129763.51060.77 | |
dc.identifier.uri | http://hdl.handle.net/10541/78776 | |
dc.description.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 microg/mL; V2, 270.2+/-114.8 microg/mL; and V3, 266.2+/-109.8 (V1 versus V2; P<0.001: V2 versus V3; 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 V2 (P<0.001), and 283.7+/-202.7 pg/mL at V3 (V2 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 V3; 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. | |
dc.language.iso | en | en |
dc.subject.mesh | Adult | |
dc.subject.mesh | Female | |
dc.subject.mesh | Growth Hormone | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Insulin-Like Growth Factor I | |
dc.subject.mesh | Male | |
dc.subject.mesh | Matrix Metalloproteinase 2 | |
dc.subject.mesh | Matrix Metalloproteinase 9 | |
dc.subject.mesh | Vascular Endothelial Growth Factor A | |
dc.title | Growth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals. | en |
dc.type | Article | en |
dc.contributor.department | Molecular Medicine Research Group, Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. hrandeva@bio.warwick.ac.uk | en |
dc.identifier.journal | Circulation | en |
html.description.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 microg/mL; V2, 270.2+/-114.8 microg/mL; and V3, 266.2+/-109.8 (V1 versus V2; P<0.001: V2 versus V3; 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 V2 (P<0.001), and 283.7+/-202.7 pg/mL at V3 (V2 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 V3; 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. |