HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M800539-JLR200v1 50/8/1538    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Navab, M. Articles by Fogelman, A. M. Search for Related Content PubMed PubMed Citation Articles by Navab, M. Articles by Fogelman, A. M. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, 1538-1547, August 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

A novel method for oral delivery of apolipoprotein mimetic peptides synthesized from all L-amino acids

Mohamad Navab^1,*, Piotr Ruchala^*, Alan J. Waring^*, Robert I. Lehrer^*, Susan Hama^*, Greg Hough^*, Mayakonda N. Palgunachari, G. M. Anantharamaiah and Alan M. Fogelman^*

^* Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1679; Atherosclerosis Research Unit
Department of Medicine, University of Alabama, Birmingham, AL 35294

¹ To whom correspondence should be addressed. e-mail: mnavab{at}mednet.ucla.edu

Administered subcutaneously, D-4F or L-4F are equally efficacious, but only D-4F is orally efficacious because of digestion of L-4F by gut proteases. Orally administering niclosamide (a chlorinated salicylanilide used as a molluscicide, antihelminthic, and lampricide) in temporal proximity to oral L-4F (but not niclosamide alone) in apoE null mice resulted in significant improvement (P < 0.001) in the HDL-inflammatory index (HII), which measures the ability of HDL to inhibit LDL-induced monocyte chemotactic activity in endothelial cell cultures. Oral administration of L-[113-122]apoJ with niclosamide also resulted in significant improvement (P < 0.001) in HII. Oral administration of niclosamide and L-4F together with pravastatin to female apoE null mice at 9.5 months of age for six months significantly reduced aortic sinus lesion area (P = 0.02), en face lesion area (P = 0.033), and macrophage lesion area (P = 0.02) compared with pretreatment, indicating lesion regression. In contrast, lesions were significantly larger in mice receiving only niclosamide and pravastatin or L-4F and pravastatin (P < 0.001). In vitro niclosamide and L-4F tightly associated rendering the peptide resistant to trypsin digestion. Niclosamide itself did not inhibit trypsin activity. The combination of niclosamide with apolipoprotein mimetic peptides appears to be a promising method for oral delivery of these peptides.—Navab, M. P., Ruchala, A. J. Waring, R. I. Lehrer, S. Hama, G. Hough, M. N. Palgunachari, G. M. Anantharamaiah, and A. M. Fogelman. A novel method for oral delivery of apolipoprotein mimetic peptides synthesized from all L-amino acids. J. Lipid Res. 2009. 50: 1538–1547.

Supplementary key words atherosclerosis • apolipoprotein A-I • apolipoprotein A-I mimetic peptides • lipoproteins • HDL

Abbreviations: apoA-I, apolipoprotein A-I; HII, HDL-inflammatory index; LPS, bacterial lipopolysaccaride; TFA, trifluroacetic acid; FTIR, Fourier transform infrared; ATR, attenuated total reflectance

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Navab, G.M. Anantharamaiah, S. T. Reddy, B. J. Van Lenten, and A. M. Fogelman HDL as a Biomarker, Potential Therapeutic Target, and Therapy Diabetes, December 1, 2009; 58(12): 2711 - 2717. [Full Text] [PDF]

				A. N. Hoofnagle and J. W. Heinecke Lipoproteomics: using mass spectrometry-based proteomics to explore the assembly, structure, and function of lipoproteins J. Lipid Res., October 1, 2009; 50(10): 1967 - 1975. [Abstract] [Full Text] [PDF]