The ApoA-I mimetic peptide FAMP promotes recovery from hindlimb ischemia through a nitric oxide (NO)-related pathway.
Int J Cardiol
; 207: 317-25, 2016 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-26814636
ABSTRACT
BACKGROUND/OBJECTIVE:
HDL has various atheroprotective functions and improves endothelial function. Apolipoprotein A-I (apoA-I) is a major protein of HDL and plays a crucial role in HDL functions. We developed a novel apoA-I mimetic peptide, FAMP (Fukuoka University ApoA-I Mimetic Peptide). It is unclear whether an apoA-I mimetic peptide can promote neovascularization in vivo. Here, we investigated the effect of FAMP on endothelial nitric oxide synthase (eNOS) activation and angiogenesis in a murine hindlimb ischemia model. METHODS ANDRESULTS:
Intramuscular administration of FAMP significantly enhanced blood flow recovery and increased capillary density in the ischemic limb of mice fed a high-cholesterol diet (HCD). In a gait analysis, FAMP ameliorated functional recovery compared with that in the control group. FAMP significantly activated Akt, ERK, and eNOS phosphorylation in endothelial cells, and improved the migratory functions of human aortic endothelial cells (HAECs). LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), significantly inhibited the activation of eNOS by FAMP. FAMP had no beneficial effects on blood flow recovery in eNOS(-/-) mice.CONCLUSIONS:
FAMP promoted recovery from hindlimb ischemia through a nitric oxide (NO)-related pathway by activation of a PI3K/Akt pathway. FAMP may become a new therapeutic agent for the future clinical treatment of critical limb ischemia (CLI).Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Apolipoproteína A-I
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Materiales Biomiméticos
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Miembro Posterior
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Isquemia
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Óxido Nítrico
Límite:
Animals
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Humans
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Male
Idioma:
En
Año:
2016
Tipo del documento:
Article