J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M800188-JLR200 on June 27, 2008

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Journal of Lipid Research, Vol. 49, 2240-2249, October 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Platelet-activating factor acetylhydrolase and transacetylase activities in human aorta and mammary artery*

Demokritos C. Tsoukatos1,*, Isabelle Brochériou§,**, Vassilios Moussis*, Christina P. Panopoulou*, Elena D. Christofidou*, Stamatis Koussissis{dagger}, Socratis Sismanidis{dagger}{dagger}, Ewa Ninio** and Stavros Siminelakis{dagger}{dagger}

* Department of Chemistry, University of Ioannina, Ioannina, Greece
{dagger} Technological Educational Institution of Athens, Athens, Greece
§ Service d'Anatomie-pathologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
** Institut national de la santé et de la recherche médicale, UMRS525, Faculté de Médecine, Université Pierre et Marie Curie, Paris, France
{dagger}{dagger} Clinic of Cardiac Surgery, University Hospital of Ioannina, Ioannina, Greece

* This work was co-funded by the European Union-European Social Fund and National Sources, in the framework of the program Pythagoras II of the Operational Program for Education and Initial Vocational Training of the 3rd Community Support Framework of the Hellenic Ministry of Education.

Published, JLR Papers in Press, June 27, 2008.

1 To whom correspondence should be addressed. e-mail: dtsoykat{at}cc.uoi.gr

Platelet-activating factor (PAF), the potent phospholipid mediator of inflammation, is involved in atherosclerosis. Platelet-activating factor-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF bioactivity, possesses both acetylhydrolase and transacetylase activities. In the present study, we measured acetylhydrolase and transacetylase activities in human atherogenic aorta and nonatherogenic mammary arteries. Immunohistochemistry analysis showed PAF-AH expression in the intima and the media of the aorta and in the media of mammary arteries. Acetylhydrolase and transacetylase activities were (mean ± SE, n = 38): acetylhydrolase of aorta, 2.8 ± 0.5 pmol/min/mg of tissue; transacetylase of aorta, 3.3 ± 0.7 pmol/min/mg of tissue; acetylhydrolase of mammary artery, 1.4 ± 0.3 pmol/min/mg of tissue (P < 0.004 as compared with acetylhydrolase of aorta); transacetylase of mammary artery, 0.8 ± 0.2 pmol/min/mg of tissue (P < 0.03 as compared with acetylhydrolase of mammary artery). Lyso-PAF accumulation and an increase in PAF bioactivity were observed in the aorta of some patients. Reverse-phase HPLC and electrospray ionization mass spectrometry analysis revealed that 1-O-hexadecyl-2 acetyl-sn glycero-3-phosphocholine accounted for 60% of the PAF bioactivity and 1-O-hexadecyl-2-butanoyl-sn-glycerol-3-phosphocholine for 40% of the PAF bioactivity. The nonatherogenic properties of mammary arteries may in part be due to low PAF formation regulated by PAF-AH activity. In atherogenic aortas, an imbalance between PAF-AH and transacetylase activity, as well as lyso-PAF accumulation, may lead to unregulated PAF formation and to progression of atherosclerosis.

Supplementary key words atherosclerosis • macrophages • smooth muscle cells • lipoproteins • atherogenesis • oxidized LDL • macrophages

Abbreviations: ESI-MS, electrospray ionization mass spectrometry; FIA, flow injection analysis; PAF, platelet-activating factor; PAF-AH, PAF-acetylhydrolase; PAF-R, PAF receptor; PC, phosphatidylcholine; PL, phospholipid; PLA2, phospholipase A2; SMC, smooth muscle cell


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