Abstract

In the past year, we have made significant progress on our work related to apolipoprotein mimetic peptides. In regard to apoA-I mimetic peptides, we finished and published in Scientific Reports our study showing that the formation of an amphipathic helix is critical for their ability to remove excess cellular cholesterol by the ABCA1 transporter. We also completed all the necessary PK and toxicology studies for the 5A apoA-I mimetic peptide. We were granted an IND by the FDA and plan to do a Phase I study in the coming year. For our project related to apoC-II mimetic peptides, which lower plasma triglycerides by activating Lipoprotein Lipase, we showed that our lead peptide lowers plasma TG by differentially activating LPL in different tissues in a model of high TG from Intralipid infusion. Results from this study will be useful for predicting possible effect of peptide for planned future clinical trial. We recently filed several patents on our new apoC-II mimetic peptides.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006095-10
Application #
10008796
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2019
Total Cost
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