© 1997 American Heart Association, Inc.
Articles |
Prostaglandin F2-Like Compounds, F2-Isoprostanes, Are Present in Increased Amounts in Human Atherosclerotic Lesions
From the Institute of Biochemistry, University Clinics Charité, Humboldt University, Hessische Str 3–4, D-10115 Berlin, F.R. Germany (C.G., J.D.M., H.K.), and the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tenn (L.J.R.).
Correspondence to Dr Hartmut Kühn, Institute for Biochemistry, University Clinics (Charité), Humboldt University, Hessische Str. 3–4, 10115 Berlin, F.R. Germany. E-mail hartmut.kuehn{at}rz.hu-berlin.de
Abstract Oxidative modification of LDL is believed to play a major role in atherogenesis. As major lipid peroxidation products oxygenated linoleic acid derivatives and oxysterols have been described in human atherosclerotic lesions. Here we report that human lesions contain isoprostanes as peroxidation products of arachidonic acid at a level of 27.1±21.2 pg/mg wet weight (n=10), which corresponds to 75.9±59.3 pg/mg dry weight. n contrast, human umbilical veins (n=10), which were used as nonatherosclerotic control vessels, contain much smaller amounts of isoprostanes (1.4±0.7 pg/mg wet weight, which corresponds to 11.7±6.2 pg/mg dry weight), and there are significant differences between the two types of vessels. As major products of linoleic acid oxidation, racemic hydroxy linoleate isomers were detected in the lesional ester lipids. In human lesions, the hydroxy linoleic acid/linoleic acid ratio was about 0.5%, a result indicating that 5 out of 1000 linoleate residues are present as hydroxylated derivatives. In umbilical veins, no hydroxy linoleic acid could be detected.
These data show that human atherosclerotic lesions contain increased amounts of hydroxy linoleic acid isomers and isoprostanes when compared with nonatherosclerotic vessel wall and suggest a link between local lipid peroxidation and progression of atherosclerosis. For evaluation of the degree of lipid peroxidation, the determination of the hydroxy linoleic acid/linoleic acid ratio appears to be more suitable than the isoprostane content.
Key Words: atherogenesis • hydroxy fatty acids • lipid peroxidation • LDL modification • cholesterol esters
This article has been cited by other articles:
 |
|
 |
|
  E. von Schlieffen, O. V. Oskolkova, G. Schabbauer, F. Gruber, S. Bluml, M. Genest, A. Kadl, C. Marsik, S. Knapp, J. Chow, et al. Multi-Hit Inhibition of Circulating and Cell-Associated Components of the Toll-Like Receptor 4 Pathway by Oxidized Phospholipids Arterioscler. Thromb. Vasc. Biol., March 1, 2009; 29(3): 356 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Yanbaeva, M. A. Dentener, E. C. Creutzberg, G. Wesseling, and E. F. M. Wouters Systemic Effects of Smoking Chest, May 1, 2007; 131(5): 1557 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Birukova, P. Fu, S. Chatchavalvanich, D. Burdette, O. Oskolkova, V. N. Bochkov, and K. G. Birukov Polar head groups are important for barrier-protective effects of oxidized phospholipids on pulmonary endothelium Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L924 - L935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Musiek, L. Gao, G. L. Milne, W. Han, M. B. Everhart, D. Wang, M. G. Backlund, R. N. DuBois, G. Zanoni, G. Vidari, et al. Cyclopentenone Isoprostanes Inhibit the Inflammatory Response in Macrophages J. Biol. Chem., October 21, 2005; 280(42): 35562 - 35570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Morrow Quantification of Isoprostanes as Indices of Oxidant Stress and the Risk of Atherosclerosis in Humans Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 279 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Miketova, K. Kaemingk, M. Hockenberry, A. Pasvogel, J. Hutter, K. Krull, and I. M. Moore Oxidative Changes in Cerebral Spinal Fluid Phosphatidylcholine during Treatment for Acute Lymphoblastic Leukemia Biol Res Nurs, January 1, 2005; 6(3): 187 - 195. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Waddington, I. B Puddey, and K. D Croft Red wine polyphenolic compounds inhibit atherosclerosis in apolipoprotein E-deficient mice independently of effects on lipid peroxidation Am. J. Clinical Nutrition, January 1, 2004; 79(1): 54 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. POLIAKOV, M.-L. BRENNAN, J. MACPHERSON, R. ZHANG, W. SHA, L. NARINE, R. G. SALOMON, and S. L. HAZEN Isolevuglandins, a novel class of isoprostenoid derivatives, function as integrated sensors of oxidant stress and are generated by myeloperoxidase in vivo FASEB J, December 1, 2003; 17(15): 2209 - 2220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Meghdadi, M. Rodrigues, A. Oguogho, R. Santler, and H. Sinzinger 8-epi-PGF 2{alpha} and 6-oxo-PGF{alpha} in Human (Varicose) Veins: Influence of Age, Sex, and Risk Factors Angiology, May 1, 2003; 54(3): 317 - 324. [Abstract] [PDF]
|
|
|
|
|
|
J. V. Higdon and B. Frei Obesity and Oxidative Stress: A Direct Link to CVD? Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 365 - 367. [Full Text] [PDF]
|
|
|
|
 |
|
 U. Riserus, S. Basu, S. Jovinge, G. N. Fredrikson, J. Arnlov, and B. Vessby Supplementation With Conjugated Linoleic Acid Causes Isomer-Dependent Oxidative Stress and Elevated C-Reactive Protein: A Potential Link to Fatty Acid-Induced Insulin Resistance Circulation, October 8, 2002; 106(15): 1925 - 1929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Huang, L. J Appel, K. D Croft, E. R Miller III, T. A Mori, and I. B Puddey Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a randomized controlled trial Am. J. Clinical Nutrition, September 1, 2002; 76(3): 549 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tintut, F. Parhami, A. Tsingotjidou, S. Tetradis, M. Territo, and L. L. Demer 8-Isoprostaglandin E2 Enhances Receptor-activated NFkappa B Ligand (RANKL)-dependent Osteoclastic Potential of Marrow Hematopoietic Precursors via the cAMP Pathway J. Biol. Chem., April 12, 2002; 277(16): 14221 - 14226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huber, H. Boechzelt, B. Karten, M. Surboeck, V. N. Bochkov, B. R. Binder, W. Sattler, and N. Leitinger Oxidized Cholesteryl Linoleates Stimulate Endothelial Cells to Bind Monocytes via the Extracellular Signal-Regulated Kinase 1/2 Pathway Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 581 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Sampson, N. Gopaul, I. R. Davies, D. A. Hughes, and M. J. Carrier Plasma F2 Isoprostanes: Direct evidence of increased free radical damage during acute hyperglycemia in type 2 diabetes Diabetes Care, March 1, 2002; 25(3): 537 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Cyrus, D. Pratico, L. Zhao, J. L. Witztum, D. J. Rader, J. Rokach, G. A. FitzGerald, and C. D. Funk Absence of 12/15-Lipoxygenase Expression Decreases Lipid Peroxidation and Atherogenesis in Apolipoprotein E-Deficient Mice Circulation, May 8, 2001; 103(18): 2277 - 2282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Thomas, S. B. Leichtweis, K. Pettersson, K. D. Croft, T. A. Mori, A. J. Brown, and R. Stocker Dietary Cosupplementation With Vitamin E and Coenzyme Q10 Inhibits Atherosclerosis in Apolipoprotein E Gene Knockout Mice Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 585 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Halvorsen, A. C. Staff, T. Henriksen, T. Sawamura, and T. Ranheim 8-iso-Prostaglandin F2{{alpha}} Increases Expression of LOX-1 in JAR Cells Hypertension, April 1, 2001; 37(4): 1184 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kaul, S. Devaraj, and I. Jialal {{alpha}}-Tocopherol and Atherosclerosis Experimental Biology and Medicine, January 1, 2001; 226(1): 5 - 12. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Mezzetti, F. Cipollone, and F. Cuccurullo Oxidative stress and cardiovascular complications in diabetes: isoprostanes as new markers on an old paradigm Cardiovasc Res, August 18, 2000; 47(3): 475 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Staff, T. Ranheim, T. Henriksen, and B. Halvorsen 8-Iso-Prostaglandin F2{alpha} Reduces Trophoblast Invasion and Matrix Metalloproteinase Activity Hypertension, June 1, 2000; 35(6): 1307 - 1313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Heller, J. R. Crowley, S. L. Hazen, D. M. Salvay, P. Wagner, S. Pennathur, and J. W. Heinecke p-Hydroxyphenylacetaldehyde, an Aldehyde Generated by Myeloperoxidase, Modifies Phospholipid Amino Groups of Low Density Lipoprotein in Human Atherosclerotic Intima J. Biol. Chem., March 31, 2000; 275(14): 9957 - 9962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Lawson, J. Rokach, and G. A. FitzGerald Isoprostanes: Formation, Analysis and Use As Indices of Lipid Peroxidation in Vivo J. Biol. Chem., August 27, 1999; 274(35): 24441 - 24444. [Full Text] [PDF]
|
|
|
|
|
|
A. D. Watson, G. Subbanagounder, D. S. Welsbie, K. F. Faull, M. Navab, M. E. Jung, A. M. Fogelman, and J. A. Berliner Structural Identification of a Novel Pro-inflammatory Epoxyisoprostane Phospholipid in Mildly Oxidized Low Density Lipoprotein J. Biol. Chem., August 27, 1999; 274(35): 24787 - 24798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Reza Mehrabi, C. Ekmekcioglu, F. Tatzber, A. Oguogho, R. Ullrich, A. Morgan, F. Tamaddon, M. Grimm, H. D Glogar, and H. Sinzinger The isoprostane, 8-epi-PGF2{alpha}, is accumulated in coronary arteries isolated from patients with coronary heart disease Cardiovasc Res, August 1, 1999; 43(2): 492 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C Carr and B. Frei Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1086 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. CARR and B. FREI Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J, June 1, 1999; 13(9): 1007 - 1024. [Abstract] [Full Text]
|
|
|
|
|
|
S. Voutilainen, J. D. Morrow, L. J. Roberts II, G. Alfthan, H. Alho, K. Nyyssonen, and J. T. Salonen Enhanced In Vivo Lipid Peroxidation at Elevated Plasma Total Homocysteine Levels Arterioscler. Thromb. Vasc. Biol., May 1, 1999; 19(5): 1263 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Witztum To E or Not To E—How Do We Tell? Circulation, December 22, 1998; 98(25): 2785 - 2787. [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Kerzee and K. S. Ramos Constitutive and Inducible Expression of Cyp1a1 and Cyp1b1 in Vascular Smooth Muscle Cells: Role of the Ahr bHLH/PAS Transcription Factor Circ. Res., September 28, 2001; 89(7): 573 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huber, H. Boechzelt, B. Karten, M. Surboeck, V. N. Bochkov, B. R. Binder, W. Sattler, and N. Leitinger Oxidized Cholesteryl Linoleates Stimulate Endothelial Cells to Bind Monocytes via the Extracellular Signal-Regulated Kinase 1/2 Pathway Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 581 - 586. [Abstract] [Full Text] [PDF]
|
|