Circulation. 2004;109:3215-3220
Published online before print June 14, 2004, doi: 10.1161/01.CIR.0000134275.90823.87
Published online before print June 14, 2004, doi: 10.1161/01.CIR.0000134275.90823.87
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;109:3215-3220.)
© 2004 American Heart Association, Inc.
Basic Science Reports |
Oral D-4F Causes Formation of Pre-ß High-Density Lipoprotein and Improves High-Density Lipoprotein–Mediated Cholesterol Efflux and Reverse Cholesterol Transport From Macrophages in Apolipoprotein E–Null Mice
From the David Geffen School of Medicine at the University of California, Los Angeles (M.N., S.T.R., S.H., G.H., V.R.G., A.C.W., J.S.F., A.M.F.), and the Department of Medicine, Atherosclerosis Research Unit, University of Alabama, Birmingham (G.M.A., G.D., D.G.).
Correspondence to Mohamad Navab, PhD, Room 47-123 CHS, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095-1679. E-mail mnavab{at}mednet.ucla.edu
Received February 10, 2004; de novo received April 13, 2004; revision received April 13, 2004; accepted May 17, 2004.
Background— These studies were designed to determine the mechanism of action of an oral apolipoprotein (apo) A-I mimetic peptide, D-4F, which previously was shown to dramatically reduce atherosclerosis in mice.
Methods and Results— Twenty minutes after 500 µg of D-4F was given orally to apoE-null mice, small cholesterol-containing particles (CCPs) of 7 to 8 nm with pre-ß mobility and enriched in apoA-I and paraoxonase activity were found in plasma. Before D-4F, both mature HDL and the fast protein liquid chromatography fractions containing the CCPs were proinflammatory. Twenty minutes after oral D-4F, HDL and CCPs became antiinflammatory, and there was an increase in HDL-mediated cholesterol efflux from macrophages in vitro. Oral D-4F also promoted reverse cholesterol transport from intraperitoneally injected cholesterol-loaded macrophages in vivo. In addition, oral D-4F significantly reduced lipoprotein lipid hydroperoxides (LOOH), except for pre-ß HDL fractions, in which LOOH increased.
Conclusions— The mechanism of action of oral D-4F in apoE-null mice involves rapid formation of CCPs, with pre-ß mobility enriched in apoA-I and paraoxonase activity. As a result, lipoprotein LOOH are reduced, HDL becomes antiinflammatory, and HDL-mediated cholesterol efflux and reverse cholesterol transport from macrophages are stimulated.
Key Words: cholesterol • lipoproteins • apolipoproteins
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. Zerrad-Saadi, P. Therond, S. Chantepie, M. Couturier, K.-A. Rye, M. J. Chapman, and A. Kontush HDL3-Mediated Inactivation of LDL-Associated Phospholipid Hydroperoxides Is Determined by the Redox Status of Apolipoprotein A-I and HDL Particle Surface Lipid Rigidity: Relevance to Inflammation and Atherogenesis Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 2169 - 2175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Wool, T. Vaisar, C. A. Reardon, and G. S. Getz An apoA-I mimetic peptide containing a proline residue has greater in vivo HDL binding and anti-inflammatory ability than the 4F peptide J. Lipid Res., September 1, 2009; 50(9): 1889 - 1900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Navab, 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., August 1, 2009; 50(8): 1538 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhang, G. Datta, Y. Zhang, A. P. Miller, P. Mochon, Y.-F. Chen, J. Chatham, G. M. Anantharamaiah, and C. R. White Apolipoprotein A-I mimetic peptide treatment inhibits inflammatory responses and improves survival in septic rats Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H866 - H873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Watanabe, V. Grijalva, S. Hama, K. Barbour, F. G. Berger, M. Navab, A. M. Fogelman, and S. T. Reddy Hemoglobin and Its Scavenger Protein Haptoglobin Associate with ApoA-1-containing Particles and Influence the Inflammatory Properties and Function of High Density Lipoprotein J. Biol. Chem., July 3, 2009; 284(27): 18292 - 18301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Peterson, D. H. Kim, M. Li, V. Positano, L. Vanella, L. F. Rodella, F. Piccolomini, N. Puri, A. Gastaldelli, C. Kusmic, et al. The L-4F mimetic peptide prevents insulin resistance through increased levels of HO-1, pAMPK, and pAKT in obese mice J. Lipid Res., July 1, 2009; 50(7): 1293 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Moreno, J. Sanz, and V. Fuster Promoting Mechanisms of Vascular Health: Circulating Progenitor Cells, Angiogenesis, and Reverse Cholesterol Transport J. Am. Coll. Cardiol., June 23, 2009; 53(25): 2315 - 2323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sattler and B. Levkau Sphingosine-1-phosphate as a mediator of high-density lipoprotein effects in cardiovascular protection Cardiovasc Res, May 1, 2009; 82(2): 201 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Navab, S. T. Reddy, B. J. Van Lenten, G. M. Anantharamaiah, and A. M. Fogelman The role of dysfunctional HDL in atherosclerosis J. Lipid Res., April 1, 2009; 50(Supplement): S145 - S149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Greaves and S. Gordon The macrophage scavenger receptor at 30 years of age: current knowledge and future challenges J. Lipid Res., April 1, 2009; 50(Supplement): S282 - S286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. K. Mishra, M. N. Palgunachari, N. R. Krishna, J. Glushka, J. P. Segrest, and G. M. Anantharamaiah Effect of Leucine to Phenylalanine Substitution on the Nonpolar Face of a Class A Amphipathic Helical Peptide on Its Interaction with Lipid: HIGH RESOLUTION SOLUTION NMR STUDIES OF 4F-DIMYRISTOYLPHOSPHATIDYLCHOLINE DISCOIDAL COMPLEX J. Biol. Chem., December 5, 2008; 283(49): 34393 - 34402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Scanu and C. Edelstein HDL: bridging past and present with a look at the future FASEB J, December 1, 2008; 22(12): 4044 - 4054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Van Lenten, A. C. Wagner, C.-L. Jung, P. Ruchala, A. J. Waring, R. I. Lehrer, A. D. Watson, S. Hama, M. Navab, G. M. Anantharamaiah, et al. Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I J. Lipid Res., November 1, 2008; 49(11): 2302 - 2311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D J Hausenloy and D M Yellon Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels Postgrad. Med. J., November 1, 2008; 84(997): 590 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. DeLeve, X. Wang, G. C. Kanel, R. D. Atkinson, and R. S. McCuskey Prevention of Hepatic Fibrosis in a Murine Model of Metabolic Syndrome with Nonalcoholic Steatohepatitis Am. J. Pathol., October 1, 2008; 173(4): 993 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Choi, A. Chae, E. Miller, M. Messig, F. Ntanios, A. N. DeMaria, S. E. Nissen, J. L. Witztum, and S. Tsimikas Relationship Between Biomarkers of Oxidized Low-Density Lipoprotein, Statin Therapy, Quantitative Coronary Angiography, and Atheroma Volume Observations From the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) Study. J. Am. Coll. Cardiol., July 1, 2008; 52(1): 24 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. deGoma, R. L. deGoma, and D. J. Rader Beyond high-density lipoprotein cholesterol levels evaluating high-density lipoprotein function as influenced by novel therapeutic approaches. J. Am. Coll. Cardiol., June 10, 2008; 51(23): 2199 - 2211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Wool, C. A. Reardon, and G. S. Getz Apolipoprotein A-I mimetic peptide helix number and helix linker influence potentially anti-atherogenic properties J. Lipid Res., June 1, 2008; 49(6): 1268 - 1283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. T. Bloedon, R. Dunbar, D. Duffy, P. Pinell-Salles, R. Norris, B. J. DeGroot, R. Movva, M. Navab, A. M. Fogelman, and D. J. Rader Safety, pharmacokinetics, and pharmacodynamics of oral apoA-I mimetic peptide D-4F in high-risk cardiovascular patients J. Lipid Res., June 1, 2008; 49(6): 1344 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D J Hausenloy and D M Yellon Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels Heart, June 1, 2008; 94(6): 706 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Movva and D. J. Rader Laboratory Assessment of HDL Heterogeneity and Function Clin. Chem., May 1, 2008; 54(5): 788 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Troutt, W. E. Alborn, M. K. Mosior, J. Dai, A. T. Murphy, T. P. Beyer, Y. Zhang, G. Cao, and R. J. Konrad An apolipoprotein A-I mimetic dose-dependently increases the formation of pre{beta}1 HDL in human plasma J. Lipid Res., March 1, 2008; 49(3): 581 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Van Lenten, A. C. Wagner, M. Navab, G. M. Anantharamaiah, S. Hama, S. T. Reddy, and A. M. Fogelman Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits J. Lipid Res., November 1, 2007; 48(11): 2344 - 2353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Weihrauch, H. Xu, Y. Shi, J. Wang, J. Brien, D. W. Jones, S. Kaul, R. A. Komorowski, M. E. Csuka, K. T. Oldham, et al. Effects of D-4F on vasodilation, oxidative stress, angiostatin, myocardial inflammation, and angiogenic potential in tight-skin mice Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1432 - H1441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. Singh, M. H. Shishehbor, and B. J. Ansell High-Density Lipoprotein as a Therapeutic Target: A Systematic Review JAMA, August 15, 2007; 298(7): 786 - 798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Watanabe, K. J. Chou, J. C. Liao, Y. Miao, H.-H. Meng, H. Ge, V. Grijalva, S. Hama, K. Kozak, G. Buga, et al. Differential Association of Hemoglobin with Proinflammatory High Density Lipoproteins in Atherogenic/Hyperlipidemic Mice: A NOVEL BIOMARKER OF ATHEROSCLEROSIS J. Biol. Chem., August 10, 2007; 282(32): 23698 - 23707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Peterson, D. Husney, A. L. Kruger, R. Olszanecki, F. Ricci, L. F. Rodella, A. Stacchiotti, R. Rezzani, J. A. McClung, W. S. Aronow, et al. Long-Term Treatment with the Apolipoprotein A1 Mimetic Peptide Increases Antioxidants and Vascular Repair in Type I Diabetic Rats J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 514 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Ng, N. Bourquard, S. Y. Hama, D. Shih, V. R. Grijalva, M. Navab, A. M. Fogelman, and S. T. Reddy Adenovirus-Mediated Expression of Human Paraoxonase 3 Protects Against the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, June 1, 2007; 27(6): 1368 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsimikas, M. Aikawa, F. J. Miller Jr, E. R. Miller, M. Torzewski, S. R. Lentz, C. Bergmark, D. D. Heistad, P. Libby, and J. L. Witztum Increased Plasma Oxidized Phospholipid:Apolipoprotein B-100 Ratio With Concomitant Depletion of Oxidized Phospholipids From Atherosclerotic Lesions After Dietary Lipid-Lowering: A Potential Biomarker of Early Atherosclerosis Regression Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 175 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Buga, J. S. Frank, G. A. Mottino, M. Hendizadeh, A. Hakhamian, J. H. Tillisch, S. T. Reddy, M. Navab, G. M. Anantharamaiah, L. J. Ignarro, et al. D-4F decreases brain arteriole inflammation and improves cognitive performance in LDL receptor-null mice on a Western diet J. Lipid Res., October 1, 2006; 47(10): 2148 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, X. Wang, C. Vales, F. Y. Lee, H. Lee, A. J. Lusis, and P. A. Edwards FXR Deficiency Causes Reduced Atherosclerosis in Ldlr-/- Mice Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2316 - 2321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Duffy and D. J. Rader Emerging Therapies Targeting High-Density Lipoprotein Metabolism and Reverse Cholesterol Transport Circulation, February 28, 2006; 113(8): 1140 - 1150. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ohashi, H. Mu, X. Wang, Q. Yao, and C. Chen Reverse cholesterol transport and cholesterol efflux in atherosclerosis QJM, December 1, 2005; 98(12): 845 - 856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Ansell, K. E. Watson, A. M. Fogelman, M. Navab, and G. C. Fonarow High-Density Lipoprotein Function: Recent Advances J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1792 - 1798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Navab, G.M. Anantharamaiah, S. T. Reddy, S. Hama, G. Hough, J. S. Frank, V. R. Grijalva, V. K. Ganesh, V. K. Mishra, M. N. Palgunachari, et al. Oral Small Peptides Render HDL Antiinflammatory in Mice and Monkeys and Reduce Atherosclerosis in ApoE Null Mice Circ. Res., September 16, 2005; 97(6): 524 - 532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gupta, L. Dai, G. Datta, D. W. Garber, H. Grenett, Y. Li, V. Mishra, M. N. Palgunachari, S. Handattu, S. H. Gianturco, et al. Inhibition of Lipopolysaccharide-Induced Inflammatory Responses by an Apolipoprotein AI Mimetic Peptide Circ. Res., August 5, 2005; 97(3): 236 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Kruger, S. Peterson, S. Turkseven, P. M. Kaminski, F. F. Zhang, S. Quan, M. S. Wolin, and N. G. Abraham D-4F Induces Heme Oxygenase-1 and Extracellular Superoxide Dismutase, Decreases Endothelial Cell Sloughing, and Improves Vascular Reactivity in Rat Model of Diabetes Circulation, June 14, 2005; 111(23): 3126 - 3134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gupta, C. R. White, S. Handattu, D. W. Garber, G. Datta, M. Chaddha, L. Dai, S. H. Gianturco, W. A. Bradley, and G.M. Anantharamaiah Apolipoprotein E Mimetic Peptide Dramatically Lowers Plasma Cholesterol and Restores Endothelial Function in Watanabe Heritable Hyperlipidemic Rabbits Circulation, June 14, 2005; 111(23): 3112 - 3118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schneider, J. L. Witztum, S. G. Young, E. H. Ludwig, E. R. Miller, S. Tsimikas, L. K. Curtiss, S. M. Marcovina, J. M. Taylor, R. M. Lawn, et al. High-level lipoprotein [a] expression in transgenic mice: evidence for oxidized phospholipids in lipoprotein [a] but not in low density lipoproteins J. Lipid Res., April 1, 2005; 46(4): 769 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Epand, R. F. Epand, B. G. Sayer, G. Datta, M. Chaddha, and G. M. Anantharamaiah Two Homologous Apolipoprotein AI Mimetic Peptides: RELATIONSHIP BETWEEN MEMBRANE INTERACTIONS AND BIOLOGICAL ACTIVITY J. Biol. Chem., December 3, 2004; 279(49): 51404 - 51414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsimikas, J. L. Witztum, E. R. Miller, W. J. Sasiela, M. Szarek, A. G. Olsson, G. G. Schwartz, and for the Myocardial Ischemia Reduction with Aggress High-Dose Atorvastatin Reduces Total Plasma Levels of Oxidized Phospholipids and Immune Complexes Present on Apolipoprotein B-100 in Patients With Acute Coronary Syndromes in the MIRACL Trial Circulation, September 14, 2004; 110(11): 1406 - 1412. [Abstract] [Full Text] [PDF]
|
|