Abstract

We previously showed that the 5A peptide can promote cholesterol efflux by the ABCA1 transporter and reduce atherosclerosis in animal models. In the past year, we showed that the peptide also has potent anti-inflammatory properties. In collaboration, with Dr. Stew Levine, we showed that the peptide had several beneficial effects in reducing inflammation in a mouse model of asthma. We recently have also shown that the 5A peptide also reduces inflammation in a chemical induced mouse model of colitis. The peptide was licensed to KineMed Inc, who received a RAID grant for performing preclinical toxicology studies, which have commenced. We have also developed a novel peptide based on last helix of apoA-I, using a hydrocarbon staple to stabilize its ability to form an amphipathic helix. The new peptide was superior to 5A in terms of its potency for effluxing cholesterol by the ABCA1 transporter and it reduced atherosclerosis in mice when given orally.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006095-03
Application #
8558035
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$663,169
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