RRC ID 44457
著者 Uehara Y, Ando S, Yahiro E, Oniki K, Ayaori M, Abe S, Kawachi E, Zhang B, Shioi S, Tanigawa H, Imaizumi S, Miura S, Saku K.
タイトル FAMP, a novel apoA-I mimetic peptide, suppresses aortic plaque formation through promotion of biological HDL function in ApoE-deficient mice.
ジャーナル J Am Heart Assoc
Abstract BACKGROUND:Apolipoprotein (apo) A-I is a major high-density lipoprotein (HDL) protein that causes cholesterol efflux from peripheral cells through the ATP-binding cassette transporter A1 (ABCA1), thus generating HDL and reversing the macrophage foam cell phenotype. Pre-β1 HDL is the smallest subfraction of HDL, which is believed to represent newly formed HDL, and it is the most active acceptor of free cholesterol. Furthermore it has a possible protective function against cardiovascular disease (CVD). We developed a novel apoA-I mimetic peptide without phospholipids (Fukuoka University ApoA-I Mimetic Peptide, FAMP).
METHODS AND RESULTS:FAMP type 5 (FAMP5) had a high capacity for cholesterol efflux from A172 cells and mouse and human macrophages in vitro, and the efflux was mainly dependent on ABCA1 transporter. Incubation of FAMP5 with human HDL or whole plasma generated small HDL particles, and charged apoA-I-rich particles migrated as pre-β HDL on agarose gel electrophoresis. Sixteen weeks of treatment with FAMP5 significantly suppressed aortic plaque formation (scrambled FAMP, 31.3 ± 8.9% versus high-dose FAMP5, 16.2 ± 5.0%; P<0.01) and plasma C-reactive protein and monocyte chemoattractant protein-1 in apoE-deficient mice fed a high-fat diet. In addition, it significantly enhanced HDL-mediated cholesterol efflux capacity from the mice.
CONCLUSIONS:A newly developed apoA-I mimetic peptide, FAMP, has an antiatherosclerotic effect through the enhancement of the biological function of HDL. FAMP may have significant atheroprotective potential and prove to be a new therapeutic tool for CVD.
巻・号 2(3)
ページ e000048
公開日 2013-5-24
DOI 10.1161/JAHA.113.000048
PII 2/3/e000048
PMID 23709562
PMC PMC3698760
MeSH Animals Aortic Diseases / prevention & control* Apolipoproteins E / deficiency Biological Transport Lipoproteins, HDL / drug effects* Lipoproteins, HDL / physiology* Male Mice Mice, Inbred C57BL Plaque, Atherosclerotic / prevention & control*
IF 4.605
引用数 33
WOS 分野 CARDIAC & CARDIOVASCULAR SYSTEMS
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)