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.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$663,169
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
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
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
Liu, Zheng; Thacker, Seth G; Fernandez-Castillejo, Sara et al. (2014) Synthesis of cholesterol analogues bearing BODIPY fluorophores by Suzuki or Liebeskind-Srogl cross-coupling and evaluation of their potential for visualization of cholesterol pools. Chembiochem 15:2087-96
Dai, Cuilian; Yao, Xianglan; Vaisman, Boris et al. (2014) ATP-binding cassette transporter 1 attenuates ovalbumin-induced neutrophilic airway inflammation. Am J Respir Cell Mol Biol 51:626-36
Vickers, Kasey C; Remaley, Alan T (2014) HDL and cholesterol: life after the divorce? J Lipid Res 55:4-12
Ditiatkovski, Michael; D'Souza, Wilissa; Kesani, Rajitha et al. (2013) An apolipoprotein A-I mimetic peptide designed with a reductionist approach stimulates reverse cholesterol transport and reduces atherosclerosis in mice. PLoS One 8:e68802
Remaley, Alan T (2013) Apolipoprotein A-II: still second fiddle in high-density lipoprotein metabolism? Arterioscler Thromb Vasc Biol 33:166-7
Vickers, Kasey C; Sethupathy, Praveen; Baran-Gale, Jeanette et al. (2013) Complexity of microRNA function and the role of isomiRs in lipid homeostasis. J Lipid Res 54:1182-91

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