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(Circulation Research. 2005;97:1085.)
© 2005 American Heart Association, Inc.

Editorials

An Apolipoprotein A-I Mimetic Works Best in the Presence of Apolipoprotein A-I

Mohamad Navab, G.M. Anantharamaiah, Alan M. Fogelman

From the David Geffen School of Medicine (M.N., A.M.F.) at the University of California, Los Angeles; and the Department of Medicine (G.M.A.), Atherosclerosis Research Unit, University of Alabama, Birmingham.

Correspondence to Mohamad Navab, PhD, Room 47-123 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095-1679. E-mail mnavab@mednet.ucla.edu

See related article, pages 1190–1197

Key Words: atherosclerosis • apolipoprotein A-I • high-density lipoprotein

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Ou et al¹ report that an apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, reduced wall thickness and improved vasoreactivity in the fascialis artery (internal diameter 180 to 240 µm) in low-density lipoprotein (LDL) receptor–null mice on a Western diet. If the mice also lacked apoA-I, D-4F improved vasoreactivity but it did not reduce wall thickness. The authors concluded that apoA-I or some critical threshold of high-density lipoprotein (HDL)-cholesterol was required for maximum effectiveness of D-4F.¹

In previous studies these authors reported that LDL caused endothelial nitric oxide synthase to produce more superoxide anion relative to nitric oxide and the balance between nitric oxide and superoxide anion was restored by the apoA-I mimetic peptide 4F.² In vivo 4F improved vasoreactivity in LDL receptor null mice fed a Western diet and in a mouse model of sickle cell disease.³ Both of these mouse models were wild-type for apoA-I.³

4F is an 18-aa peptide that has no sequence homology with apoA-I but forms a class A amphipathic helix and mimics the lipid binding properties of apoA-I.⁴ Oral administration of 4F synthesized from all D-amino acids (D-4F) has been shown to dramatically reduce atherosclerosis in mouse models with wild-type apoA-I.⁵ Oral D-4F synergized with pravastatin to increase intestinal apoA-I synthesis and increase plasma apoA-I levels and caused lesion regression in old apoE-null mice.⁶

Oral administration of D-4F to apoE-null or C57BL/6 mice caused the formation of small cholesterol-containing particles with pre-ß mobility that were enriched in apoA-I and paraoxonase activity, rendered HDL antiinflammatory, and promoted . . . [Full Text of this Article]

Related Article:

Effects of D-4F on Vasodilation and Vessel Wall Thickness in Hypercholesterolemic LDL Receptor–Null and LDL Receptor/Apolipoprotein A-I Double-Knockout Mice on Western Diet

Jingsong Ou, Jingli Wang, Hao Xu, Zhijun Ou, Mary G. Sorci-Thomas, Deron W. Jones, Paul Signorino, John C. Densmore, Sushma Kaul, Keith T. Oldham, and Kirkwood A. Pritchard, Jr
Circ. Res. 2005 97: 1190-1197. [Abstract] [Full Text] [PDF]