One of the most important developments in the LT area relates to atherogenesis where several different studies have implicated LTs in disease progression . 5-LO, FLAP and LTA4 hydrolase are expressed in human atherosclerotic lesions . LTB4 stimulates the expression of genes related to atherogenesis in rat basophilic leukemia cells . Using mouse genetic models of atherogenesis (apo-E_/_ or LDLR_/_), the treatment with LTB4 antagonists , the deletion of 5-LO  and deletion of the BLT1 receptor  were found to reduce disease severity. The 5-LO gene was identified as part of the gene cluster on chromosome 6 conferring resistance to atherogenesis in the mouse strain CAST . A congenic strain, containing the athero-resistant chromosome 6 region, was found to express 5-LO at reduced levels . The deduced sequence for 5-LO from the atherosclerosis resistant mice contained mutations that affected enzyme activity when introduced into the human enzyme . A polymorphism in the 5-LO gene promoter has recently been identified in relation to increased atherosclerosis .
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