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

2.50
Hdl Handle:
http://hdl.handle.net/10541/78776
Title:
Growth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals.
Authors:
Randeva, Harpal S; Lewandowski, Krzysztof C; Komorowski, Jan; Murray, Robert D; O'Callaghan, Chris J; Hillhouse, Edward W; Stepien, Henryk; Shalet, Stephen M
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.
Affiliation:
Molecular Medicine Research Group, Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. hrandeva@bio.warwick.ac.uk
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
Journal:
Circulation
Issue Date:
25-May-2004
URI:
http://hdl.handle.net/10541/78776
DOI:
10.1161/01.CIR.0000129763.51060.77
PubMed ID:
15123527
Type:
Article
Language:
en
ISSN:
1524-4539
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorRandeva, Harpal S-
dc.contributor.authorLewandowski, Krzysztof C-
dc.contributor.authorKomorowski, Jan-
dc.contributor.authorMurray, Robert D-
dc.contributor.authorO'Callaghan, Chris J-
dc.contributor.authorHillhouse, Edward W-
dc.contributor.authorStepien, Henryk-
dc.contributor.authorShalet, Stephen M-
dc.date.accessioned2009-08-26T16:22:46Z-
dc.date.available2009-08-26T16:22:46Z-
dc.date.issued2004-05-25-
dc.identifier.citationGrowth 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 Circulationen
dc.identifier.issn1524-4539-
dc.identifier.pmid15123527-
dc.identifier.doi10.1161/01.CIR.0000129763.51060.77-
dc.identifier.urihttp://hdl.handle.net/10541/78776-
dc.description.abstractBACKGROUND: 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.en
dc.language.isoenen
dc.subject.meshAdult-
dc.subject.meshFemale-
dc.subject.meshGrowth Hormone-
dc.subject.meshHumans-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshMale-
dc.subject.meshMatrix Metalloproteinase 2-
dc.subject.meshMatrix Metalloproteinase 9-
dc.subject.meshVascular Endothelial Growth Factor A-
dc.titleGrowth hormone replacement decreases plasma levels of matrix metalloproteinases (2 and 9) and vascular endothelial growth factor in growth hormone-deficient individuals.en
dc.typeArticleen
dc.contributor.departmentMolecular Medicine Research Group, Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. hrandeva@bio.warwick.ac.uken
dc.identifier.journalCirculationen

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