Details

Autor(en) / Beteiligte

• Suematsu, Yasunori
• Kawachi, Emi
• Idemoto, Yoshiaki
• Matsuo, Yoshino
• Kuwano, Takashi
• Kitajima, Ken
• Imaizumi, Satoshi
• Kawamura, Akira
• Saku, Keijiro
• Uehara, Yoshinari
• Miura, Shin-ichiro

Titel

Anti-atherosclerotic effects of an improved apolipoprotein A-I mimetic peptide

Ist Teil von

• International journal of cardiology, 2019-12, Vol.297, p.111-117

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Apolipoprotein (Apo)A-I is a major protein component of high-density lipoprotein (HDL) that causes cholesterol efflux from peripheral cells through ATP-binding cassette transporter A1 (ABCA1) and the generation of HDL. Furthermore, it has a possible protective function against atherosclerotic cardiovascular disease (ASCVD). We previously developed a novel ApoA-I mimetic peptide without phospholipids (Fukuoka University ApoA-I Mimetic Peptide, FAMP). According to our previous studies, FAMP had an anti-arteriosclerotic effect. Since the required dose and reaction time of conventional FAMP were relatively large and short, respectively, we newly developed an improved FAMP (i-FAMP). We synthesized four candidate i-FAMPs, i-FAMP-D1, -D2, -D3 and -D4, and examined which i-FAMP has greater cholesterol efflux capacity than FAMP in A172 human glioblastoma cells transiently transfected with human ABCA1 cDNA. Only i-FAMP-D1 showed significantly greater cholesterol efflux capacity than conventional FAMP. i-FAMP-D1 formed stronger α-helical conformations than FAMP as assessed by circular dichroism spectra. Thus, we selected i-FAMP-D1 for further experiments. i-FAMP-D1 had a greater atheroprotective effect than FAMP in ApoE knockout mice. In addition, i-FAMP-D1 activated cholesterol efflux from macrophage to HDL more strongly than FAMP and increased cholesterol excretion from liver to feces. These results suggest that i-FAMP-D1 has a stronger anti-atherosclerotic effect than conventional FAMP. •Apolipoprotein (Apo)A-I is a major protein component of high-density lipoprotein.•We newly developed an improved Fukuoka University ApoA-I Mimetic Peptide (i-FAMP-D1).•i-FAMP-D1 formed stronger α-helical conformations and had a superior atheroprotective effect in ApoE knockout mice.•i-FAMP-D1 activated cholesterol efflux from macrophage to HDL and increased cholesterol excretion from liver to feces.