|
Journal of Lipid Research, Vol. 42, 545-552, April 2001
Copyright © 2001 by Lipid Research, Inc.
A new synthetic class A amphipathic peptide analogue protects mice from diet-induced atherosclerosis
David W. Garbera,
Geeta Dattaa,
Manjula Chaddhaa,
M. N. Palgunacharia,
Susan Y. Hamab,
Mohamad Navabb,
Alan M. Fogelmanb,
Jere P. Segresta, and
G. M. Anantharamaiaha
a The Atherosclerosis Research Unit and the Departments of Medicine and Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294
b Atherosclerosis Research Unit, University of California at Los Angeles Cardiology, Los Angeles, CA 90095
Correspondence to:
G. M. Anantharamaiah, To whom correspondence should be addressed., ananth{at}uab.edu (E-mail)
Several synthetic class A peptide analogues have been shown to mimic many of the properties of human apo A-I in vitro. A new peptide [acetyl-(AspTrpLeuLysAlaPheTyrAspLysValPheGluLysPheLysGluPhePhe)-NH2; 5F], with increased amphipathicity, was administered by intraperitoneal injection, 20 µg/day for 16 weeks, to C57BL/6J mice fed an atherogenic diet. Mouse apo A-I (MoA-I) (50 µg/day) or phosphate-buffered saline (PBS) injections were given to other mice as controls. Total plasma cholesterol levels and lipoprotein profiles were not significantly different between the treated and control groups, except that the mice receiving 5F or MoA-I had lower high density lipoprotein (HDL) cholesterol when calculated as a percentage of total cholesterol. No toxicity or production of antibodies to the injected materials was observed. When HDL was isolated from high fat diet-administered mice injected with 5F and presented to human artery wall cells in vitro together with human low density lipoprotein (LDL), there were substantially fewer lipid hydroperoxides formed and substantially less LDL-induced monocyte chemotactic activity than with HDL from PBS-injected animals. Injection of human apo A-I produced effects similar to 5F on lipid peroxide formation and LDL-induced monocyte chemotactic activity, but injection of MoA-I was significantly less effective in reducing lipid hydroperoxide formation or lowering LDL-induced monocyte chemotactic activity. Mice receiving peptide 5F had significantly less aortic atherosclerotic lesion area compared with mice receiving PBS, whereas lesion area in mice receiving MoA-I was similar to that of the PBS-injected animals. This is the first in vivo demonstration that a model class A amphipathic helical peptide has antiatherosclerotic properties.
We conclude that 5F inhibits lesion formation in high fat diet-administered mice by a mechanism that does not involve changes in the lipoprotein profile, and may have potential in the prevention and treatment of atherosclerosis. Garber, D. W., G. Datta, M. Chaddha, M. N. Palgunachari, S. Y. Hama, M. Navab, A. M. Fogelman, J. P. Segrest, and G. M. Anantharamaiah. A new synthetic class A amphipathic peptide analogue protects mice from diet-induced atherosclerosis. J. Lipid Res. 2001. 42: 545;552.
Supplementary key words:
cholesterol, lipoproteins, metabolism, aorta

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
I. N. Baranova, A. V. Bocharov, T. G. Vishnyakova, R. Kurlander, Z. Chen, D. Fu, I. M. Arias, G. Csako, A. P. Patterson, and T. L. Eggerman
CD36 Is a Novel Serum Amyloid A (SAA) Receptor Mediating SAA Binding and SAA-induced Signaling in Human and Rodent Cells
J. Biol. Chem.,
March 12, 2010;
285(11):
8492 - 8506.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Navab, I. Shechter, G.M. Anantharamaiah, S. T. Reddy, B. J. Van Lenten, and A. M. Fogelman
Structure and Function of HDL Mimetics
Arterioscler Thromb Vasc Biol,
February 1, 2010;
30(2):
164 - 168.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Frias, U. Lang, C. Gerber-Wicht, and R. W. James
Native and reconstituted HDL protect cardiomyocytes from doxorubicin-induced apoptosis
Cardiovasc Res,
January 1, 2010;
85(1):
118 - 126.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
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. A. Frias, R. W. James, C. Gerber-Wicht, and U. Lang
Native and reconstituted HDL activate Stat3 in ventricular cardiomyocytes via ERK1/2: Role of sphingosine-1-phosphate
Cardiovasc Res,
May 1, 2009;
82(2):
313 - 323.
[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]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
G. M. Anantharamaiah, V. K. Mishra, D. W. Garber, G. Datta, S. P. Handattu, M. N. Palgunachari, M. Chaddha, M. Navab, S. T. Reddy, J. P. Segrest, et al.
Structural requirements for antioxidative and anti-inflammatory properties of apolipoprotein A-I mimetic peptides
J. Lipid Res.,
September 1, 2007;
48(9):
1915 - 1923.
[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]
|
 |
|

|
 |

|
 |
 
S. P. Handattu, D. W. Garber, D. C. Horn, D. W. Hughes, B. Berno, A. D. Bain, V. K. Mishra, M. N. Palgunachari, G. Datta, G. M. Anantharamaiah, et al.
ApoA-I Mimetic Peptides with Differing Ability to Inhibit Atherosclerosis Also Exhibit Differences in Their Interactions with Membrane Bilayers
J. Biol. Chem.,
January 19, 2007;
282(3):
1980 - 1988.
[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]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
M. Navab, G.M. Anantharamaiah, S. T. Reddy, B. J. Van Lenten, A. C. Wagner, S. Hama, G. Hough, E. Bachini, D. W. Garber, V. K. Mishra, et al.
An Oral ApoJ Peptide Renders HDL Antiinflammatory in Mice and Monkeys and Dramatically Reduces Atherosclerosis in Apolipoprotein E-Null Mice
Arterioscler Thromb Vasc Biol,
September 1, 2005;
25(9):
1932 - 1937.
[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]
|
 |
|

|
 |

|
 |
 
M. Navab, G.M. Anantharamaiah, S. T. Reddy, S. Hama, G. Hough, V. R. Grijalva, N. Yu, B. J. Ansell, G. Datta, D. W. Garber, et al.
Apolipoprotein A-I Mimetic Peptides
Arterioscler Thromb Vasc Biol,
July 1, 2005;
25(7):
1325 - 1331.
[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]
|
 |
|

|
 |

|
 |
 
N. Dashti, G. Datta, M. Manchekar, M. Chaddha, and G. M. Anantharamaiah
Model class A and class L peptides increase the production of apoA-I-containing lipoproteins in HepG2 cells
J. Lipid Res.,
October 1, 2004;
45(10):
1919 - 1928.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Li, K.-Y. Chyu, J. R. F. Neto, J. Yano, N. Nathwani, C. Ferreira, P. C. Dimayuga, B. Cercek, S. Kaul, and P. K. Shah
Differential Effects of Apolipoprotein A-I-Mimetic Peptide on Evolving and Established Atherosclerosis in Apolipoprotein E-Null Mice
Circulation,
September 21, 2004;
110(12):
1701 - 1705.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. V. Bocharov, I. N. Baranova, T. G. Vishnyakova, A. T. Remaley, G. Csako, F. Thomas, A. P. Patterson, and T. L. Eggerman
Targeting of Scavenger Receptor Class B Type I by Synthetic Amphipathic {alpha}-Helical-containing Peptides Blocks Lipopolysaccharide (LPS) Uptake and LPS-induced Pro-inflammatory Cytokine Responses in THP-1 Monocyte Cells
J. Biol. Chem.,
August 20, 2004;
279(34):
36072 - 36082.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Navab, G.M. Anantharamaiah, S. T. Reddy, S. Hama, G. Hough, V. R. Grijalva, A. C. Wagner, J. S. Frank, G. Datta, D. Garber, et al.
Oral D-4F Causes Formation of Pre-{beta} High-Density Lipoprotein and Improves High-Density Lipoprotein-Mediated Cholesterol Efflux and Reverse Cholesterol Transport From Macrophages in Apolipoprotein E-Null Mice
Circulation,
June 29, 2004;
109(25):
3215 - 3220.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Datta, R. F. Epand, R. M. Epand, M. Chaddha, M. A. Kirksey, D. W. Garber, S. Lund-Katz, M. C. Phillips, S. Hama, M. Navab, et al.
Aromatic Residue Position on the Nonpolar Face of Class A Amphipathic Helical Peptides Determines Biological Activity
J. Biol. Chem.,
June 18, 2004;
279(25):
26509 - 26517.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Navab, G. M. Ananthramaiah, S. T. Reddy, B. J. Van Lenten, B. J. Ansell, G. C. Fonarow, K. Vahabzadeh, S. Hama, G. Hough, N. Kamranpour, et al.
Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL
J. Lipid Res.,
June 1, 2004;
45(6):
993 - 1007.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. L. Macdonald, T. L. Terry, L. B. Agellon, P. N. Nation, and G. A. Francis
Administration of Tyrosyl Radical-Oxidized HDL Inhibits the Development of Atherosclerosis in Apolipoprotein E-Deficient Mice
Arterioscler Thromb Vasc Biol,
September 1, 2003;
23(9):
1583 - 1588.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. J. Bisoendial, G. K. Hovingh, J. H.M. Levels, P. G. Lerch, I. Andresen, M. R. Hayden, J. J.P. Kastelein, and E. S.G. Stroes
Restoration of Endothelial Function by Increasing High-Density Lipoprotein in Subjects With Isolated Low High-Density Lipoprotein
Circulation,
June 17, 2003;
107(23):
2944 - 2948.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Ou, Z. Ou, D. W. Jones, S. Holzhauer, O. A. Hatoum, A. W. Ackerman, D. W. Weihrauch, D. D. Gutterman, K. Guice, K. T. Oldham, et al.
L-4F, an Apolipoprotein A-1 Mimetic, Dramatically Improves Vasodilation in Hypercholesterolemia and Sickle Cell Disease
Circulation,
May 13, 2003;
107(18):
2337 - 2341.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Ou, J. Ou, A. W. Ackerman, K. T. Oldham, and K. A. Pritchard Jr
L-4F, an Apolipoprotein A-1 Mimetic, Restores Nitric Oxide and Superoxide Anion Balance in Low-Density Lipoprotein-Treated Endothelial Cells
Circulation,
March 25, 2003;
107(11):
1520 - 1524.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Navab, G.M. Anantharamaiah, S. Hama, D. W. Garber, M. Chaddha, G. Hough, R. Lallone, and A. M. Fogelman
Oral Administration of an Apo A-I Mimetic Peptide Synthesized From D-Amino Acids Dramatically Reduces Atherosclerosis in Mice Independent of Plasma Cholesterol
Circulation,
January 22, 2002;
105(3):
290 - 292.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. W. Castellani and A. J. Lusis
ApoA-II Versus ApoA-I: Two for One Is Not Always a Good Deal
Arterioscler Thromb Vasc Biol,
December 1, 2001;
21(12):
1870 - 1872.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Navab, B. J. Van Lenten, S. T. Reddy, and A. M. Fogelman
High-Density Lipoprotein and the Dynamics of Atherosclerotic Lesions
Circulation,
November 13, 2001;
104(20):
2386 - 2387.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. L. Haddox, R. R. Pfister, C. I. Sommers, J. E. Blalock, and M. Villain
Inhibitory Effect of a Complementary Peptide on Ulceration in the Alkali-Injured Rabbit Cornea
Invest. Ophthalmol. Vis. Sci.,
November 1, 2001;
42(12):
2769 - 2775.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Datta, M. Chaddha, S. Hama, M. Navab, A. M. Fogelman, D. W. Garber, V. K. Mishra, R. M. Epand, R. F. Epand, S. Lund-Katz, et al.
Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide
J. Lipid Res.,
July 1, 2001;
42(7):
1096 - 1104.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Datta, D. W. Garber, B. H. Chung, M. Chaddha, N. Dashti, W. A. Bradley, S. H. Gianturco, and G. M. Anantharamaiah
Cationic domain 141-150 of apoE covalently linked to a class A amphipathic helix enhances atherogenic lipoprotein metabolism in vitro and in vivo
J. Lipid Res.,
June 1, 2001;
42(6):
959 - 966.
[Abstract]
[Full Text]
|
 |
|
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|