Growth hormone-releasing peptide-2 suppresses vascular oxidative stress in ApoE-/- mice but does not reduce atherosclerosis.
GH-releasing peptide-2 (GHRP-2) is a synthetic peptide that increases circulating GH and IGF-I levels. It also binds to CD36, a scavenger receptor for oxidized low-density lipoprotein (OxLDL), and may prevent cellular uptake of this proatherogenic complex. To determine its potential antiatherogenic effects, GHRP-2 (20 microg twice daily) was administered sc to ApoE(-/-) mice for 12 wk. GHRP-2 increased circulating IGF-I 1.2- to 1.6-fold and decreased circulating interferon-gamma by 66%. Although GHRP-2 did not alter atherosclerotic plaque area, it decreased aortic production of superoxide as assessed by dihydroethidium staining. GHRP-2 decreased aortic gene expression of 12/15-lipoxygenase by 92% and reduced the aortic expression of interferon-gamma and macrophage migration inhibitory factor. In cultured aortic smooth muscle cells, GHRP-2 prevented the OxLDL-induced generation of peroxides, down-regulation of IGF-I receptor, and apoptosis. In macrophages, GHRP-2 reduced lipid accumulation with OxLDL exposure. In summary, GHRP-2 exerts antioxidant effects in vivo and in vitro but does not reduce plaque burden. The lack of an antiatherogenic effect may be due to GH-dependent effects in vivo, thereby blunting the effect of increased IGF-I.
Titterington
Jane S
JS
Section of Endocrinology, Tulane University Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Sukhanov
Sergiy
S
Higashi
Yusuke
Y
Vaughn
Charlotte
C
Bowers
Cyril
C
Delafontaine
Patrice
P
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007371:Interferon-gamma / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010545:Peroxides / Q000378:metabolism
D001057:Apolipoproteins E; D016207:Cytokines; D009842:Oligopeptides; D010545:Peroxides; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma; C091874:growth hormone-releasing peptide-2; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase