Myocardial infarction (MI heart attack) is one of the leading causes of death in the world, according to background information in the article. The researchers in this study previously reported the identification of a gene variant that predisposes patients to MI. The gene encodes the 5-lipoxygenase activating protein (FLAP) and its risk variant results in an almost 2-fold increased risk of MI.
Hakon Hakonarson, M.D., Ph.D., of Decode genetics Inc., Reykjavik, Iceland and colleagues conducted a study to determine whether the biological perturbation (disruption) caused by the gene variants that predispose patients to MI through the leukotriene (an inflammatory protein) pathway could be compensated by inhibiting FLAP. The branch of the leukotriene pathway linked to risk of MI, through the activity of FLAP, leads to the production of leukotriene B4, which is a potent mediator of arterial inflammation. The researchers' previously published findings indicate that MI patients, both those with and without the at-risk variants of the FLAP gene, produce more leukotriene B4 than do controls. This suggests that the up-regulation of the leukotriene pathway contributes to risk of the disease, both through genetic and environmental factors, primarily, the researchers believe, by promoting inflammation in atherosclerotic plaques and increasing their propensity to rupture. By inhibiting the function of FLAP and thereby down-regulating the activity of the leukotriene pathway, the risk of MI may be decreased. Of several available inhibitors of FLAP, the researchers used DG-031, which had been used in asthma clinical trials and was shown to be safe and well-tolerated.
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