The ApoA-I mimetic peptide FAMP promotes recovery from hindlimb ischemia through a nitric oxide (NO)-related pathway

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• 作者：Kohei Takata^a ; ¹ ; Satoshi Imaizumi^a ; ¹ ; ^{simaizumi@fukuoka-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Emi Kawachi^a ; Eiji Yahiro^a ; Yasunori Suematsu^a ; Tomohiko Shimizu^a ; Satomi Abe^a ; Yoshino Matsuo^a ; Kyoko Nakajima^b ; Tetsuhiko Yasuno^c ; Shiro Jimi^d ; Bo Zhang^e ; Yoshinari Uehara^a ; Shin-ichiro Miura^a ; Keijiro Saku^a
• 关键词：Apolipoprotein A-I mimetic peptide ; High-density lipoprotein ; Endothelial nitric oxide synthase
• 刊名：International Journal of Cardiology
• 出版年：2016
• 出版时间：15 March 2016
• 年：2016
• 卷：207
• 期：Complete
• 页码：317-325
• 全文大小：1320 K

文摘

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 and results

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).