Lipoprotein-Associated Phospholipase A 2 , Platelet-Activating Factor Acetylhydrolase, Is Expressed by Macrophages in Human and Rabbit Atherosclerotic Lesions
| Autor: | David G. Tew, Simon Q.J. Rice, Tomi Häkkinen, Kari Karkola, Lisa Patel, Jukka Luoma, Mikko Hiltunen, Colin H. Macphee, Kevin J. Milliner, Seppo Ylä-Herttuala |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Arteriosclerosis Lipoproteins Polymerase Chain Reaction Gene Expression Regulation Enzymologic Muscle Smooth Vascular Phospholipases A chemistry.chemical_compound Phospholipase A2 Animals Humans RNA Messenger Enzyme Inhibitors Aorta In Situ Hybridization Aged chemistry.chemical_classification Phospholipase A Platelet-activating factor biology Macrophages Lipoprotein-associated phospholipase A2 Fatty acid Middle Aged 1-Alkyl-2-acetylglycerophosphocholine Esterase Molecular biology Lipoproteins LDL Antisense Elements (Genetics) Lysophosphatidylcholine Microscopy Fluorescence chemistry Biochemistry Sulfoxides biology.protein Azetidines Female lipids (amino acids peptides and proteins) Rabbits Cardiology and Cardiovascular Medicine Lipoprotein |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 19:2909-2917 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.19.12.2909 |
| Popis: | Abstract —We studied the expression of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), an enzyme capable of hydrolyzing platelet-activating factor (PAF), PAF-like phospholipids, and polar-modified phosphatidylcholines, in human and rabbit atherosclerotic lesions. Oxidative modification of low-density lipoprotein, which plays an important role in atherogenesis, generates biologically active PAF-like modified phospholipid derivatives with polar fatty acid chains. PAF is known to have a potent proinflammatory activity and is inactivated by its hydrolysis. On the other hand, lysophosphatidylcholine and oxidized fatty acids released from oxidized low-density lipoprotein as a result of Lp-PLA 2 activity are thought to be involved in the progression of atherosclerosis. Using combined in situ hybridization and immunocytochemistry, we detected Lp-PLA 2 mRNA and protein in macrophages in both human and rabbit atherosclerotic lesions. Reverse transcriptase—polymerase chain reaction analysis indicated an increased expression of Lp-PLA 2 mRNA in human atherosclerotic lesions. In addition, ≈6-fold higher Lp-PLA 2 activity was detected in atherosclerotic aortas of Watanabe heritable hyperlipidemic rabbits compared with normal aortas from control rabbits. It is concluded that (1) macrophages in both human and rabbit atherosclerotic lesions express Lp-PLA 2 , which could cleave any oxidatively modified phosphatidylcholine present in the lesion area, and (2) modulation of Lp-PLA 2 activity could lead to antiatherogenic effects in the vessel wall. |
| Databáze: | OpenAIRE |
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