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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1140.)
© 2003 American Heart Association, Inc.

Editorials

5-Lipoxygenase-Derived Leukotrienes

Mediators Also of Atherosclerotic Inflammation

Olof Rådmark

From the Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.

Correspondence to Dr Olof Rådmark, Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, S-17177 Stockholm, Sweden.

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

Atherogenesis is now viewed as the outcome of hypercholesterolemia in combination with inflammation of the vessel wall; an intertwined sequence of events leads to fatty streaks, which may develop to atherosclerosis.¹ Several recent studies have implicated lipoxygenases in this process. Mammalian lipoxygenases have two principal functions.² One is to modify membranes by peroxidation reactions; 12/15-lipoxygenases (12/15-LOs, in homo 15-LO type 1) is typically connected with this function. The other is to produce signaling lipid mediators which exert effects via G protein–coupled plasma membrane–bound receptors; maybe the best example is 5-lipoxygenase (5LO) and the leukotrienes.^3,4 Accordingly, lipoxygenases can in principle contribute to the pathophysiology of atherosclerosis in two ways: by LDL oxidation and by biosynthesis of proinflammatory leukotrienes. The first articles indicating a role for 12/15-LO in oxidative modification of LDL appeared 10 years ago,^5,6 for a recent review discussing pro- and anti-atherogenic effects of 12/15-LO, see the article by Funk and Cyrus.⁷ In the June issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Kühn et al⁸ present data showing that mutations in 5LO occurring in atherosclerosis-resistant CAST/CON6 mice reduces the activity of 5LO in vitro. Here, recent findings which support of a role for 5LO and leukotrienes in atherosclerotic inflammation are discussed.

See page 1072, June 2003

The only mammalian lipoxygenase which has been structurally determined is the rabbit reticulocyte 15-lipoxygenase (a 12/15-LO).⁹ Based on this crystal structure, the 5LO structure can be modeled (Figure) as a monomeric enzyme with two domains. The dominating catalytic C-terminal domain contains . . . [Full Text of this Article]

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