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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1248.)
© 2002 American Heart Association, Inc.

Editorials

The Hunt for Nutritional and Pharmacological Modulators of Paraoxonase

P.N. Durrington; B. Mackness; M.I. Mackness

From the University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom.

Correspondence to Dr P.N. Durrington, University Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. E-mail pdurrington@man.ac.uk

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Considerable experimental evidence suggests that lipid peroxides on LDL and their breakdown products are responsible for the physical changes in the LDL particle and the fragmentation of its apolipoprotein B, which permit it to bind to a wide range of high-affinity receptors on cells in the arterial wall, such as endothelial cells, macrophages, and smooth muscle cells, which are key players in atherosclerosis.¹ Fat-soluble antioxidant vitamins in vitro delay the oxidation of LDL,² suggesting that they might have the therapeutic potential to protect against coronary heart disease (CHD). However, now that several clinical trials of antioxidant fat-soluble vitamins have been completed, the reality is that they do not prevent coronary or other atherosclerotic events.^2–4 The reasons for this have been reviewed,⁵ but germane to the issue may be that the protection against oxidation afforded to LDL by fat-soluble antioxidants is relatively short lived, being principally in the extension of the early lag phase in lipid peroxidation (conjugated diene formation) by a matter of minutes. They act as antioxidants only when they are more susceptible to oxidation than the molecules they protect, and once oxidized, they can become pro-oxidants.² Additionally, erosion of their potential benefit may stem from their effect in increasing cholesteryl ester heteroexchange^6,7 which is increasingly being viewed as proatherogenic.^8–10 It could explain the amelioration by high-dose antioxidant vitamins of the regression of coronary atheroma induced by lipid-lowering drugs.¹¹

See page 1329

Paraoxonase 1 (PON1), located on HDL, was first shown more than a decade ago to protect in . . . [Full Text of this Article]

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