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Lipoprotein-Associated Phospholipase A 2 , Platelet-Activating Factor Acetylhydrolase, Is Expressed by Macrophages in Human and Rabbit Atherosclerotic Lesions
Abstract
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.
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Cited by
Dennis, E. A., Cao, J., Hsu, Y.-H., Magrioti, V., & Kokotos, G. (2011) · Chemical Reviews · doi:10.1021/cr200085w · Cited by 1,203
Jellinger, P. S., Handelsman, Y., Rosenblit, P. D., Bloomgarden, Z. T., Fonseca, V. A., Garber, A. J., Grunberger, G., Guerin, C. K., Bell, D. S. H., Mechanick, J. I., et al. (2017) · Endocrine Practice · doi:10.4158/ep171764.appgl · Cited by 1,094
An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases
Law, S.-H., Chan, M.-L., Marathe, G. K., Parveen, F., Chen, C.-H., & Ke, L.-Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051149 · Cited by 817
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O’Donoghue, M. L., Braunwald, E., White, H. D., Steen, D. P., Lukas, M. A., Tarka, E., Steg, P. G., Hochman, J. S., Bode, C., Maggioni, A. P., et al. (2014) · JAMA · doi:10.1001/jama.2014.11061 · Cited by 456
Metadata
- Authors
- Häkkinen, T., Luoma, J. S., Hiltunen, M. O., Macphee, C. H., Milliner, K. J., Patel, L., Rice, S. Q., Tew, D. G., Karkola, K., & Ylä-Herttuala, S.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 1999-12
- Volume
- 19
- Issue
- 12
- Pages
- 2909-2917
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2152460160
- Cited by
- 239
- References
- 0
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Lipoprotein-Associated Phospholipase A 2 , Platelet-Activating Factor Acetylhydrolase, Is Expressed by Macrophages in Human and Rabbit Atherosclerotic Lesions. https://app.cochat.ai/papers/10.1161/01.atv.19.12.2909
- The paper
- Häkkinen, T., Luoma, J. S., Hiltunen, M. O., Macphee, C. H., Milliner, K. J., Patel, L., Rice, S. Q., Tew, D. G., Karkola, K., & Ylä-Herttuala, S. (1999). Lipoprotein-Associated Phospholipase A 2 , Platelet-Activating Factor Acetylhydrolase, Is Expressed by Macrophages in Human and Rabbit Atherosclerotic Lesions. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/01.atv.19.12.2909
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