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Growth Hormone‐Releasing Peptide‐2 reduces oxidative stress in ApoE ‐/‐ mice but does not reduce atherosclerosis
Author(s) -
Titterington Jane S.,
Sukhanov Sergiy,
Vaughn Charlotte,
Delafontaine Patrick
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.626.23
Subject(s) - cd36 , medicine , endocrinology , downregulation and upregulation , oxidative stress , chemistry , growth factor , scavenger receptor , receptor , in vivo , lipoprotein , biology , biochemistry , cholesterol , microbiology and biotechnology , gene
Growth Hormone‐Releasing Peptide‐2 (GHRP‐2) is a synthetic peptide that increases circulating Growth Hormone and Insulin‐Like Growth Factor‐1 (IGF‐1) 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 µg BID) was administered subcutaneously to ApoE ‐/‐ mice for 12 weeks. GHRP‐2 increased circulating IGF‐1 1.2‐1.6 fold and decreased circulating interferon‐γ (IFN‐γ) by 66%. While GHRP‐2 did not alter atherosclerotic plaque area, it decreased aortic production of superoxide as assessed by DHE staining. GHRP‐2 decreased aortic gene expression of 15‐lipoxygenase by 92% and reduced the aortic expression of IFN‐γ, Cu/Zn superoxide dismutase, macrophage migration inhibitory factor, and IGF‐1 receptor (IGF‐1R). In cultured aortic smooth muscle cells, GHRP‐2 prevented the OxLDL‐induced generation of peroxides, downregulation of IGF‐1R, 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 antiatherogenic effect may be due to the inability of GHRP‐2 to prevent OxLDL‐induced downregulation of IGF‐1R in vivo , thereby blunting the effect of increased IGF‐1. Funding: NIH HL070241