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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:805.)
© 2008 American Heart Association, Inc.

Editorials

Cysteinyl-Leukotrienes in Cerebrovascular Disease

Angels and Demons?

Magnus Bäck

From the Department of Cardiology and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.

Correspondence to Magnus Bäck, MD, PhD, CMM L8:03, Karolinska University Hospital, 171 76 Stockholm, Sweden. E-mail Magnus.Back@ki.se

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

Although the initial interest in the field of leukotriene (LT) research was focused on their potent bronchoconstrictive effects, subsequent studies have suggested LTs as key mediators in several inflammatory diseases. Genetic variations within the enzymes transforming arachidonic acid into LTs (Figure) have for example been associated with atherosclerosis and an increased risk of cardiovascular events.¹

View larger version (22K):   Figure Metabolism of arachidonic acid into leukotrienes (LTs) by 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP), LTA4 hydrolase (LTA4H), and LTC4 synthase (LTC4S). Cysteinyl-LTs (LTC4, LTD4, LTE4) activate CysLT receptors, which can be targeted by antiasthmatic CysLT1 receptor antagonists. Inset shows the 5 exons (I-V) of the LTC4S gene and its 5'-flanking untranscribed region (UTR). The 2 reported single nucleotide polymorphisms (SNP) are located at 444 and 1072 bp upstream, respectively. The –444 A to C substitution has been associated with increased LTC4 synthesis in eosinophils,6 aspirin intolerant asthma,5 increased risk for coronary calcium,10 increased carotid artery intima media thickness (IMT),10 and a decreased risk of ischemic cerebrovascular events.4

See accompanying article on page 990

Leukotriene C₄ synthase (LTC₄S; Figure) is a microsomal glutathione-S-transferase (mGST), which conjugates LTA₄ with glutathione.² The product, LTC₄, shares its following enzymatic steps with glutathione to yield LTD₄ and LTE₄ (Figure). These 3 LTs, collectively referred to as the cysteinyl-LTs, exert their actions by means of at least 2 subclasses of CysLT receptors (Figure) expressed in airway and vessels, as well as on inflammatory cells.³ The . . . [Full Text of this Article]

Related Article:

Promotor Polymorphisms in Leukotriene C₄ Synthase and Risk of Ischemic Cerebrovascular Disease

Jacob J. Freiberg, Anne Tybjærg-Hansen, Henrik Sillesen, Gorm B. Jensen, and Børge G. Nordestgaard
Arterioscler Thromb Vasc Biol 2008 28: 990-996. [Abstract] [Full Text] [PDF]