Abstract

In the past year we developed and published a paper on a novel apolipoprotein mimetic peptide based on apoC-II. It is a bi-helical peptide containing a class TypeA aphipathic helix as the first helix, which enables it to bind to lipoproteins. The second helix is based on the Lipoprotein Lipase (LPL) activation domain of apoC-II. The peptide showed equimolar potency in activating LPL compared to the full length apoC-II protein. We also created a novel mouse model of apoC-II deficiency, which had a hypertriglyceridemic phenotype. Treatment of the mice with the peptide lowered serum triglycerides over 90% for up to 2 days when the peptide was delivered subcutaneously. Unexpectedly the apoC-II KO mice over time became obese and insulin resistance. We are currently investigating whether increased lipolysis by apoC-II preferentially favors delivery of fatty acids to skeletal muscle. If so, it suggests that this peptide may have utility for lowering post-prandial lipids in diabetic patients. The peptide is now being licensed to an outside company.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006095-06
Application #
9157410
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
U.S. National Heart Lung and Blood Inst
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