Abstract

The 5A amphipathic peptide, which was shown earlier by our laboratory to be specific for removing cholesterol by the ABCA1 transporter, was tested in a mouse model of atherosclerosis and was found to be protective (ref. 1). In a rabbit vascular collar model, it was found to reduce inflammation (ref. 4). In collaboration with Dr. Stewart Levine, we showed in a mouse model of asthma, it also reduced inflammation associated with asthma (J Immunol 2011;86:576). In the past year, we have also developed new single helical peptides containing a hydrocarbon staple that enhanced the cholesterol efflux potential of these peptides and made them resistant to gastric and intestinal proteolysis, thus potentially making these peptides orally available (BBRC 2011:10:446). The 5A peptide was licensed to an outside company for further drug development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006095-02
Application #
8344890
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2011
Total Cost
$688,623
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Islam, Rafique M; Pourmousa, Mohsen; Sviridov, Denis et al. (2018) Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux. Sci Rep 8:2956
Karathanasis, Sotirios K; Freeman, Lita A; Gordon, Scott M et al. (2017) The Changing Face of HDL and the Best Way to Measure It. Clin Chem 63:196-210
Wolska, Anna; Dunbar, Richard L; Freeman, Lita A et al. (2017) Apolipoprotein C-II: New findings related to genetics, biochemistry, and role in triglyceride metabolism. Atherosclerosis 267:49-60
Ditiatkovski, Michael; Palsson, Jonatan; Chin-Dusting, Jaye et al. (2017) Apolipoprotein A-I Mimetic Peptides: Discordance Between In Vitro and In Vivo Properties-Brief Report. Arterioscler Thromb Vasc Biol 37:1301-1306
Gordon, Scott M; Remaley, Alan T (2017) High density lipoproteins are modulators of protease activity: Implications in inflammation, complement activation, and atherothrombosis. Atherosclerosis 259:104-113
Gordon, Scott M; Pourmousa, Mohsen; Sampson, Maureen et al. (2017) Identification of a novel lipid binding motif in apolipoprotein B by the analysis of hydrophobic cluster domains. Biochim Biophys Acta Biomembr 1859:135-145
Jin, Xueting; Sviridov, Denis; Liu, Ying et al. (2016) ABCA1 (ATP-Binding Cassette Transporter A1) Mediates ApoA-I (Apolipoprotein A-I) and ApoA-I Mimetic Peptide Mobilization of Extracellular Cholesterol Microdomains Deposited by Macrophages. Arterioscler Thromb Vasc Biol 36:2283-2291
Remaley, Alan T (2015) HDL cholesterol/HDL particle ratio: a new measure of HDL function? J Am Coll Cardiol 65:364-6
Sviridov, Dmitri; Remaley, Alan T (2015) High-density lipoprotein mimetics: promises and challenges. Biochem J 472:249-59
Amar, Marcelo J A; Sakurai, Toshihiro; Sakurai-Ikuta, Akiko et al. (2015) A novel apolipoprotein C-II mimetic peptide that activates lipoprotein lipase and decreases serum triglycerides in apolipoprotein E-knockout mice. J Pharmacol Exp Ther 352:227-35

Showing the most recent 10 out of 30 publications