The role of oxidized phospholipids in atherosclerosis

被引:277
作者
Berliner, Judith A. [1 ,2 ]
Leitinger, Norbert [3 ,4 ]
Tsimikas, Sotirios [5 ]
机构
[1] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA
[2] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA
[3] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA
[4] Univ Virginia, Robert Berne Ctr Cardiovasc Res, Charlottesville, VA USA
[5] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA
基金
美国国家卫生研究院;
关键词
endothelial; macrophage; smooth muscle cells; clinical trials; SMOOTH-MUSCLE-CELLS; LOW-DENSITY-LIPOPROTEIN; MINIMALLY MODIFIED LDL; OXIDATION-PRODUCTS; ENDOTHELIAL-CELLS; CARDIOVASCULAR-DISEASE; APOPTOTIC CELLS; INNATE IMMUNITY; IN-VIVO; EXPRESSION;
D O I
10.1194/jlr.R800074-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
There is increasing evidence that oxidized phospholipids (OxPLs) play an important role in atherosclerosis. These phospholipids accumulate in human and mouse lesions. Specific OxPLs have been identified as major regulators of many cell types present in the vessel wall. In endothelial cells, >1,000 genes are regulated. Some of these genes are pro-atherogenic and others anti-atherogenic. The anti-atherogenic effects are likely important in slowing the atherogenic process. Several receptors and signaling pathways associated with OxPL action have been identified and shown to be upregulated in human lesions. A structural model of the mechanism by which specific OxPLs serve as CD36 ligands has been identified. Specific oxidized phospholipids are also present in plasma and associated with Lp(a) particles. In humans, OxPL/apolipoprotein B has been shown to be a prognostic indicator and a separate risk factor for coronary events. Levels of OxPL in plasma have been shown to be correlated with platelet activation. jlr The results of these studies suggest an important role for OxPL in all stages of atherosclerosis. Berliner, J. A., N. Leitinger, and S. Tsimikas. The role of oxidized phospholipids in atherosclerosis. J. Lipid Res. 2009. S207-S212.
引用
收藏
页码:S207 / S212
页数:6
相关论文
共 49 条
[21]   Oxidized phosphatidylserine-CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells [J].
Greenberg, Michael E. ;
Sun, Mingjiang ;
Zhang, Renliang ;
Febbraio, Maria ;
Silverstein, Roy ;
Hazen, Stanley L. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (12) :2613-2625
[22]   Modification of LDL with oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) results in a novel form of minimally modified LDL that modulates gene expression in macrophages [J].
Groeneweg, Mathijs ;
Vergouwe, Monique N. ;
Scheffer, Peter G. ;
Vermue, Hendrikus P. A. ;
Gelpke, Maarten D. Sollewijn ;
Sijbers, Anneke M. ;
Leitinger, Norbert ;
Hofker, Marten H. ;
de Winther, Menno P. J. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2008, 1781 (6-7) :336-343
[23]   Protein targets of oxidized phospholipids in endothelial cells [J].
Gugiu, B. Gabriel ;
Mouiflesseaux, Kevin ;
Duong, Victoria ;
Herzog, Tabitha ;
Hekimian, Avetis ;
Koroniak, Lukasz ;
Vondriska, Thomas M. ;
Watson, Andrew D. .
JOURNAL OF LIPID RESEARCH, 2008, 49 (03) :510-520
[24]   OXIDATIVELY MODIFIED LDL CONTAINS PHOSPHOLIPIDS WITH PLATELET-ACTIVATING FACTOR-LIKE ACTIVITY AND STIMULATES THE GROWTH OF SMOOTH-MUSCLE CELLS [J].
HEERY, JM ;
KOZAK, M ;
STAFFORINI, DM ;
JONES, DA ;
ZIMMERMAN, GA ;
MCINTYRE, TM ;
PRESCOTT, SM .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (05) :2322-2330
[25]   Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury [J].
Imai, Yumiko ;
Kuba, Keiji ;
Neely, G. Greg ;
Yaghubian-Malhami, Rubina ;
Perkmann, Thomas ;
van Loo, Geert ;
Ermolaeva, Maria ;
Veldhuizen, Ruud ;
Leung, Y. H. Connie ;
Wang, Hongliang ;
Liu, Haolin ;
Sun, Yang ;
Pasparakis, Manolis ;
Kopf, Manfred ;
Mech, Christin ;
Bavari, Sina ;
Peiris, J. S. Malik ;
Slutsky, Arthur S. ;
Akira, Shizuo ;
Hultqvist, Malin ;
Holmdahl, Rikard ;
Nicholls, John ;
Jiang, Chengyu ;
Binder, Christoph J. ;
Penninger, Josef M. .
CELL, 2008, 133 (02) :235-249
[26]   Oxidized phospholipids alter vascular connexin expression, phosphorylation, and heterocellular communication [J].
Isakson, Brant E. ;
Kronke, Gerhard ;
Kadl, Alexandra ;
Leitinger, Norbert ;
Duling, Brian R. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (10) :2216-2221
[27]   Oxidized phospholipids, lipoprotein(a), lipoprotein-associated phospholipase a2 activity, and 10-year cardiovascular outcomes - Prospective results from the Bruneck study [J].
Kiechl, Stefan ;
Willeit, Johann ;
Mayr, Manuel ;
Viehweider, Brigitte ;
Oberhollenzer, Martin ;
Kronenberg, Florian ;
Wiedermann, Christian J. ;
Oberthaler, Sabine ;
Xu, Qingbo ;
Witztum, Joseph L. ;
Tsimikas, Sotirios .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2007, 27 (08) :1788-1795
[28]   Reduced connexin43 expression inhibits atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice [J].
Kwak, BR ;
Veillard, N ;
Pelli, G ;
Mulhaupt, F ;
James, RW ;
Chanson, M ;
Mach, F .
CIRCULATION, 2003, 107 (07) :1033-1039
[29]   Ox-PAPC activation of PMET system increases expression of heme oxygenase-1 in human aortic endothelial cell [J].
Lee, Sangderk ;
Li, Rongsong ;
Kim, Brandon ;
Palvolgyi, Roland ;
Ho, Tiffany ;
Yang, Qian-Zhou ;
Xu, Jason ;
Szeto, Wan Lam ;
Honda, Henry ;
Berliner, Judith A. .
JOURNAL OF LIPID RESEARCH, 2009, 50 (02) :265-274
[30]   Oxidized phospholipids as triggers of inflammation in atherosclerosis [J].
Leitinger, N .
MOLECULAR NUTRITION & FOOD RESEARCH, 2005, 49 (11) :1063-1071