Apolipoprotein E mimetic Peptide dramatically lowers plasma cholesterol and restores endothelial function in watanabe heritable hyperlipidemic rabbits.

Academic Article

Abstract

  • BACKGROUND: These studies were designed to determine whether the dual-domain peptide with a class A amphipathic helix linked to the receptor-binding domain of apolipoprotein (apo) E (Ac-hE-18A-NH2) possesses both antidyslipidemic and antiinflammatory properties. METHODS AND RESULTS: A single bolus (15 mg/kg IV) of Ac-hE-18A-NH2 that contains LRKLRKRLLR (141- to 150-residue region of apo E) covalently linked to apo A-I mimetic peptide 18A not only reduced plasma cholesterol levels (baseline, 562+/-29.0 mg/dL versus 287.7+/-22.0 mg/dL at 18 hours, P<0.001) in the Watanabe heritable hyperlipidemic rabbit model but also significantly improved arterial endothelial function. This improvement was associated with a reduction in 2 markers of oxidative stress. First, the plasma lipid hydroperoxide content was reduced significantly, an effect associated with a 5-fold increase in HDL paraoxonase activity. Second, the formation of superoxide anion, a scavenger of nitric oxide, was also significantly reduced in arteries of these animals. CONCLUSIONS: Because dyslipidemia and endothelial dysfunction are common features of the atherosclerotic disease process, this unique dual-domain peptide has ideal composite properties that ameliorate key contributory factors to atherosclerosis.
  • Published In

  • Circulation  Journal
  • Keywords

  • Animals, Apolipoproteins E, Atherosclerosis, Cholesterol, Endothelium, Vascular, Hyperlipidemias, Inflammation, Lipid Metabolism, Inborn Errors, Lipids, Male, Molecular Mimicry, Oxidative Stress, Peptide Fragments, Peptides, Rabbits, Superoxides
  • Digital Object Identifier (doi)

    Author List

  • Gupta H; White CR; Handattu S; Garber DW; Datta G; Chaddha M; Dai L; Gianturco SH; Bradley WA; Anantharamaiah GM
  • Start Page

  • 3112
  • End Page

  • 3118
  • Volume

  • 111
  • Issue

  • 23