The LO Road to Atherosclerosis

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Science  16 Jan 2004:
Vol. 303, Issue 5656, pp. 289
DOI: 10.1126/science.303.5656.289c

Lipoxygenases (LOs) are a family of enzymes that are attracting attention because of their role in the biosynthesis of lipids that mediate inflammatory and allergic reactions. Inhibitors of these enzymes are already in clinical use for treatment of asthma. Because lipid-mediated inflammatory circuits are also etiologic factors in atherosclerosis, Dwyer et al. investigated whether genetically determined variation in LOs might contribute to vascular disease. In a pilot study of 470 healthy individuals, they found that two variant alleles of the gene encoding 5-LO were associated with an increase in carotid artery intima-media thickness, an established indicator of systemic atherosclerosis. Notably, the effects of these variant alleles appeared to be modified by dietary intake of certain types of fatty acids, such as those in marine fish. This study and a recent mouse analysis linking a different LO gene to osteoporosis (see Reports, 9 January 2004, p. 229) broaden the scope of disorders that are potentially treatable with drugs targeting these enzymes. — PAK

N. Engl. J. Med. 350, 29 (2004).

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