| A new HDL mimetic peptide that stimulates cellular cholesterol efflux with high efficiency greatly reduces atherosclerosis in mice. | |
| | |
MedLine Citation:
|
PMID: 20075422 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Here, we report the creation of a single-helix peptide (ATI-5261) that stimulates cellular cholesterol efflux with K(m) molar efficiency approximating native apolipoproteins. Anti-atherosclerosis activity of ATI-5261 was evaluated in LDLR(-/-) and apolipoprotein (apo)E(-/-) mice approximately 5-7 months of age, following 13-18 weeks on a high-fat Western diet (HFWD). Treatment of fat-fed LDLR(-/-) mice with daily intraperitoneal injections of ATI-5261 (30 mg/kg) for 6 weeks reduced atherosclerosis by 30%, as judged by lesion area covering the aorta (7.9 +/- 2 vs.11.3 +/- 2.5% control, P = 0.011) and lipid-content of aortic sinus plaque (25 +/- 5.8 vs. 33 +/- 4.9% control, P = 0.014). In apoE(-/-) mice, the peptide administered 30 mg/kg ip on alternate days for 6 weeks reduced atherosclerosis by approximately 45% (lesion area = 15 +/- 7 vs. 25 +/- 8% control, P = 0.00016; plaque lipid-content = 20 +/- 6 vs. 32 +/- 8% control, P < 0.0001). Similar reductions in atherosclerosis were achieved using ATI-5261:POPC complexes. Single intraperitoneal injection of ATI-5261 increased reverse cholesterol transport from macrophage foam-cells to feces over 24-48 h. In summary, relatively short-term treatment of mice with the potent cholesterol efflux peptide ATI-5261 reduced substantial atherosclerosis. This was achieved using an L-amino acid peptide, in the presence of severe hypercholesterolemia/HFWD, and did not require daily injections or formulation with phospholipids when administered via intraperitoneal injection. |
| | |
Authors:
|
John K Bielicki; Haiyan Zhang; Yuan Cortez; Ying Zheng; Vasanthy Narayanaswami; Arti Patel; Jan Johansson; Salman Azhar |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-01-14 |
Journal Detail:
|
Title: Journal of lipid research Volume: 51 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2010 Jun |
Date Detail:
|
Created Date: 2010-05-12 Completed Date: 2010-08-17 Revised Date: 2012-01-19 |
Medline Journal Info:
|
Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
|
Languages: eng Pagination: 1496-503 Citation Subset: IM |
Affiliation:
|
Lawrence Berkeley National Laboratory, Donner Laboratory, MS1-267, University of California, Berkeley, CA 94720, USA. jkbielicki@lbl.gov |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Apolipoproteins E / chemistry Atherosclerosis / complications, drug therapy, metabolism*, pathology* Biological Transport / drug effects Biomimetic Materials / chemical synthesis, chemistry, pharmacology*, therapeutic use Cholesterol / metabolism* Drug Design Hyperlipidemias / complications Lipoproteins, HDL / metabolism* Macrophages / drug effects, metabolism, pathology Male Mice Molecular Sequence Data Peptides / chemical synthesis, chemistry, pharmacology*, therapeutic use Protein Structure, Secondary Protein Structure, Tertiary Solubility |
| Grant Support | |
ID/Acronym/Agency:
|
HL092473/HL/NHLBI NIH HHS; R01 HL033881-24/HL/NHLBI NIH HHS; R01 HL033881-26/HL/NHLBI NIH HHS; R01 HL092473-03/HL/NHLBI NIH HHS; R01 HL092473-04/HL/NHLBI NIH HHS; R01-HL033881/HL/NHLBI NIH HHS; R21 HL085791-02/HL/NHLBI NIH HHS; R21-HL085791/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Apolipoproteins E; 0/Lipoproteins, HDL; 0/Peptides; 57-88-5/Cholesterol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Intronic CArG box regulates cysteine-rich protein 2 expression in the adult but not in developing va...
Next Document: Compassion Fatigue: What Is It? Why Does It Matter? Recognizing the Symptoms, Acknowledging the Impa...