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Paraoxonases in Inflammation, Infection, and Toxicology pp 99–111Cite as

Paraoxonase 1 Attenuates Human Plaque Atherogenicity: Relevance to the Enzyme Lactonase Activity

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 660))

Abstract

Human atherosclerotic lesions contain a variety of lipids and oxidized lipids, which can induce atherogenic properties such as macrophage oxidation, lipoprotein oxidation and inhibition of cholesterol efflux from macrophages. These atherogenic properties of the plaque’s lipid fraction are associated with the inhibition of paraoxonase 1 (PON1) lactonase activity. In contrast, incubation of PON1 with the plaque’s lipid fraction reduces the lesion’s atherogenic properties by lowering the capacity of the oxidized lipids to induce further oxidation. The mechanism of PON1’s protective action and its endogenous substrate however remain elusive. Modeling studies may characterize PON1’s possible active site, and help envisage the structure of potential endogenous and exogenous lactones as PON1 ligands. Such modeling thus may lead to a better understanding of PON1’s anti-atherogenic mechanism of action.

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Abbreviations

CVD:

cardiovascular disease

EtAc:

ethyl acetate

HDL:

high density lipoprotein

7-keto-ch:

7-ketocholesterol

LDL:

low density lipoproteins

LE:

lesion extract

LT:

N-linoleoyl tyrosine

LTG:

N-linoleoyl tyrosine 2’-deoxyguanosyl ester

MPM:

mouse peritoneal macrophages

7-OH-ch:

7-hydroxycholesterols

7-OOH-ch:

7-hydroperoxycholesterols

OS:

oxidative-stress

Ox-LDL:

oxidized low density lipoproteins

PON1:

paraoxonase 1

rePON1:

recombinant PON1

TBARS:

thiobarbituric acid-reactive substance

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Authors and Affiliations

  1. The Lipid Research Laboratory, Technion Faculty of Medicine, Rappaport Family Institute for Research in the Medical Science and Rambam Medical Center, 31096, Haifa, Israel

    Hagai Tavori & Michael Aviram

  2. Laboratory of Natural Medicinal Compounds, MIGAL – Galilee Technology Center, Tel Hai College, 11016, 831, Kiryat Shmona, Israel

    Hagai Tavori & Jacob Vaya

Authors
  1. Hagai Tavori
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  2. Jacob Vaya
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  3. Michael Aviram
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Correspondence to Hagai Tavori .

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Editors and Affiliations

  1. Division of Cardiology, University of California, Los Angeles, Le Conte Ave. 10833, Los Angeles, 90095-1679, U.S.A.

    Srinivasa T. Reddy

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Tavori, H., Vaya, J., Aviram, M. (2010). Paraoxonase 1 Attenuates Human Plaque Atherogenicity: Relevance to the Enzyme Lactonase Activity. In: Reddy, S. (eds) Paraoxonases in Inflammation, Infection, and Toxicology. Advances in Experimental Medicine and Biology, vol 660. Humana Press. https://doi.org/10.1007/978-1-60761-350-3_10

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