on July 1, 2002
Circulation. 2002
Published online before print July 1, 2002, doi: 10.1161/01.CIR.0000023623.87083.4F
Published online before print July 1, 2002, doi: 10.1161/01.CIR.0000023623.87083.4F
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 15, 2002
From the Department of Medicine (A.T., Y.-R.X., X.-P.W., Y.-S.S., C.P., L.W.C., A.J.L., D.M.S.), the Department of Microbiology, Immunology, and Molecular Genetics (A.T., A.J.L.), and the Department of Human Genetics (A.J.L.), University of California, Los Angeles. A. Tward is now at the University of California, San Francisco. * To whom correspondence should be addressed. E-mail: dshih{at}mednet.ucla.edu.
Background—Serum paraoxonase (PON1), an enzyme carried on HDL, inhibits LDL oxidation, and in human population studies, low PON1 activity is associated with atherosclerosis. In addition, PON1 knockout mice are more susceptible to lipoprotein oxidation and atherosclerosis. To evaluate whether PON1 protects against atherosclerosis and lipid oxidation in a dose-dependent manner, we generated and studied human PON1 transgenic mice. Methods and Results—Human PON1 transgenic mice were produced by using bacterial artificial chromosome genomic clones. The mice had 2- to 4-fold increased plasma PON1 levels, but plasma cholesterol levels were unchanged. Atherosclerotic lesions were significantly reduced in the transgenic mice when both dietary and apoE-null mouse models were used. HDL isolated from the transgenic mice also protected against LDL oxidation more effectively. Conclusions—Our results indicate that PON1 protects against atherosclerosis in a dose-dependent manner and suggest that it may be a potential target for developing therapeutic agents for the treatment of cardiovascular disease.
Revised on May 4, 2002
Accepted on May 6, 2002
Decreased Atherosclerotic Lesion Formation in Human Serum Paraoxonase Transgenic Mice
Aaron Tward MA,
Key words: antioxidants • lipoproteins • free radicals • atherosclerosis • genes
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 T. Bhattacharyya, S. J. Nicholls, E. J. Topol, R. Zhang, X. Yang, D. Schmitt, X. Fu, M. Shao, D. M. Brennan, S. G. Ellis, et al. Relationship of Paraoxonase 1 (PON1) Gene Polymorphisms and Functional Activity With Systemic Oxidative Stress and Cardiovascular Risk JAMA, March 19, 2008; 299(11): 1265 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Van Eck, M. Hoekstra, R. B. Hildebrand, Y. Yaong, D. Stengel, J. K. Kruijt, W. Sattler, U. J.F. Tietge, E. Ninio, T. J.C. Van Berkel, et al. Increased Oxidative Stress in Scavenger Receptor BI Knockout Mice With Dysfunctional HDL Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2413 - 2419. [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]
|
|
|
|
 |
|
 D. M. Shih, Y.-R. Xia, X.-P. Wang, S. S. Wang, N. Bourquard, A. M. Fogelman, A. J. Lusis, and S. T. Reddy Decreased Obesity and Atherosclerosis in Human Paraoxonase 3 Transgenic Mice Circ. Res., April 27, 2007; 100(8): 1200 - 1207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Horke, I. Witte, P. Wilgenbus, M. Kruger, D. Strand, and U. Forstermann Paraoxonase-2 Reduces Oxidative Stress in Vascular Cells and Decreases Endoplasmic Reticulum Stress-Induced Caspase Activation Circulation, April 17, 2007; 115(15): 2055 - 2064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Ng, N. Bourquard, V. Grijalva, S. Hama, D. M. Shih, M. Navab, A. M. Fogelman, A. J. Lusis, S. Young, and S. T. Reddy Paraoxonase-2 Deficiency Aggravates Atherosclerosis in Mice Despite Lower Apolipoprotein-B-containing Lipoproteins: ANTI-ATHEROGENIC ROLE FOR PARAOXONASE-2 J. Biol. Chem., October 6, 2006; 281(40): 29491 - 29500. [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]
|
|
|
|
|
|
C. Y. Han, T. Chiba, J. S. Campbell, N. Fausto, M. Chaisson, G. Orasanu, J. Plutzky, and A. Chait Reciprocal and Coordinate Regulation of Serum Amyloid A Versus Apolipoprotein A-I and Paraoxonase-1 by Inflammation in Murine Hepatocytes Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1806 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Mackness, R. Quarck, W. Verreth, M. Mackness, and P. Holvoet Human Paraoxonase-1 Overexpression Inhibits Atherosclerosis in a Mouse Model of Metabolic Syndrome Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1545 - 1550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Graner, R. W. James, J. Kahri, M. S. Nieminen, M. Syvanne, and M.-R. Taskinen Association of Paraoxonase-1 Activity and Concentration With Angiographic Severity and Extent of Coronary Artery Disease J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2429 - 2435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Carlson, P. J. Heagerty, T. S. Hatsukami, R. J. Richter, J. Ranchalis, J. Lewis, T. J. Bacus, L. A. McKinstry, G. D. Schellenberg, M. Rieder, et al. TagSNP analyses of the PON gene cluster: effects on PON1 activity, LDL oxidative susceptibility, and vascular disease J. Lipid Res., May 1, 2006; 47(5): 1014 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rosenblat, L. Gaidukov, O. Khersonsky, J. Vaya, R. Oren, D. S. Tawfik, and M. Aviram The Catalytic Histidine Dyad of High Density Lipoprotein-associated Serum Paraoxonase-1 (PON1) Is Essential for PON1-mediated Inhibition of Low Density Lipoprotein Oxidation and Stimulation of Macrophage Cholesterol Efflux J. Biol. Chem., March 17, 2006; 281(11): 7657 - 7665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ahmed, G. Orasanu, V. Nehra, L. Asatryan, D. J. Rader, O. Ziouzenkova, and J. Plutzky High-Density Lipoprotein Hydrolysis by Endothelial Lipase Activates PPAR{alpha}: A Candidate Mechanism for High-Density Lipoprotein-Mediated Repression of Leukocyte Adhesion Circ. Res., March 3, 2006; 98(4): 490 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Shih, H. R. Kast-Woelbern, J. Wong, Y.-R. Xia, P. A. Edwards, and A. J. Lusis A role for FXR and human FGF-19 in the repression of paraoxonase-1 gene expression by bile acids J. Lipid Res., February 1, 2006; 47(2): 384 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gutierrez, E. P. Ratliff, A. M. Andres, X. Huang, W. L. McKeehan, and R. A. Davis Bile Acids Decrease Hepatic Paraoxonase 1 Expression and Plasma High-Density Lipoprotein Levels Via FXR-Mediated Signaling of FGFR4 Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 301 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Rozek, T. S. Hatsukami, R. J. Richter, J. Ranchalis, K. Nakayama, L. A. McKinstry, D. A. Gortner, E. Boyko, G. D. Schellenberg, C. E. Furlong, et al. The correlation of paraoxonase (PON1) activity with lipid and lipoprotein levels differs with vascular disease status J. Lipid Res., September 1, 2005; 46(9): 1888 - 1895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bradshaw, A. Gutierrez, J. H. Miyake, K. R. Davis, A. C. Li, C. K. Glass, L. K. Curtiss, and R. A. Davis Facilitated replacement of Kupffer cells expressing a paraoxonase-1 transgene is essential for ameliorating atherosclerosis in mice PNAS, August 2, 2005; 102(31): 11029 - 11034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Rodriguez-Esparragon, J. C. Rodriguez-Perez, Y. Hernandez-Trujillo, A. Macias-Reyes, A. Medina, A. Caballero, and C. M. Ferrario Allelic Variants of the Human Scavenger Receptor Class B Type 1 and Paraoxonase 1 on Coronary Heart Disease: Genotype-Phenotype Correlations Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 854 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chait, C. Y. Han, J. F. Oram, and J. W. Heinecke Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease? J. Lipid Res., March 1, 2005; 46(3): 389 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Teiber, D. I. Draganov, and B. N. La Du Purified human serum PON1 does not protect LDL against oxidation in the in vitro assays initiated with copper or AAPH J. Lipid Res., December 1, 2004; 45(12): 2260 - 2268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gouedard, R. Barouki, and Y. Morel Induction of the Paraoxonase-1 Gene Expression by Resveratrol Arterioscler. Thromb. Vasc. Biol., December 1, 2004; 24(12): 2378 - 2383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Barter, S. Nicholls, K.-A. Rye, G.M. Anantharamaiah, M. Navab, and A. M. Fogelman Antiinflammatory Properties of HDL Circ. Res., October 15, 2004; 95(8): 764 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Lusis, A. M. Fogelman, and G. C. Fonarow Genetic Basis of Atherosclerosis: Part I: New Genes and Pathways Circulation, September 28, 2004; 110(13): 1868 - 1873. [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]
|
|
|
|
 |
|
 C. Gouedard, R. Barouki, and Y. Morel Dietary Polyphenols Increase Paraoxonase 1 Gene Expression by an Aryl Hydrocarbon Receptor-Dependent Mechanism Mol. Cell. Biol., June 15, 2004; 24(12): 5209 - 5222. [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]
|
|
|
|
|
|
J. Lie, R. de Crom, T. van Gent, R. van Haperen, L. Scheek, F. Sadeghi-Niaraki, and A. van Tol Elevation of plasma phospholipid transfer protein increases the risk of atherosclerosis despite lower apolipoprotein B-containing lipoproteins J. Lipid Res., May 1, 2004; 45(5): 805 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Connelly, G. F. Maguire, and D. I. Draganov Separation and quantitative recovery of mouse serum arylesterase and carboxylesterase activity J. Lipid Res., March 1, 2004; 45(3): 561 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kontush, E. C. de Faria, S. Chantepie, and M. J. Chapman Antioxidative Activity of HDL Particle Subspecies Is Impaired in Hyperalphalipoproteinemia: Relevance of Enzymatic and Physicochemical Properties Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 526 - 533. [Abstract] [Full Text]
|
|
|
|
|
|
M. Rosenblat, T. Hayek, K. Hussein, and M. Aviram Decreased Macrophage Paraoxonase 2 Expression in Patients With Hypercholesterolemia Is the Result of Their Increased Cellular Cholesterol Content: Effect of Atorvastatin Therapy Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 175 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Deakin, I. Leviev, S. Guernier, and R. W. James Simvastatin Modulates Expression of the PON1 Gene and Increases Serum Paraoxonase: A Role for Sterol Regulatory Element-Binding Protein-2 Arterioscler. Thromb. Vasc. Biol., November 1, 2003; 23(11): 2083 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. Cabana, C. A. Reardon, N. Feng, S. Neath, J. Lukens, and G. S. Getz Serum paraoxonase: effect of the apolipoprotein composition of HDL and the acute phase response J. Lipid Res., April 1, 2003; 44(4): 780 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rosenblat, D. Draganov, C. E. Watson, C. L. Bisgaier, B. N. La Du, and M. Aviram Mouse Macrophage Paraoxonase 2 Activity Is Increased Whereas Cellular Paraoxonase 3 Activity Is Decreased Under Oxidative Stress Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 468 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Rozenberg, D. M. Shih, and M. Aviram Human Serum Paraoxonase 1 Decreases Macrophage Cholesterol Biosynthesis: Possible Role for Its Phospholipase-A2-Like Activity and Lysophosphatidylcholine Formation Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 461 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Marathe, G. A. Zimmerman, and T. M. McIntyre Platelet-activating Factor Acetylhydrolase, and Not Paraoxonase-1, Is the Oxidized Phospholipid Hydrolase of High Density Lipoprotein Particles J. Biol. Chem., January 31, 2003; 278(6): 3937 - 3947. [Abstract] [Full Text] [PDF]
|
|