Re: debate

Re: paper #3 - leukotrienes, genome and atherosclerosis

This paper showed that people with genetic anomaly (6% of the study group) with two allele for 5-lipoxygenase expression (TWO-5LOX) had 11% thicker atherosclerotic lesions (IMT). Allegedly due to increased leukotrienes production. 11% isn't a huge effect though it is significant. However, it doesn't really answer the question of are leaukotrienes really the cause or are they the effect of atherosclerosis. More placque buildup may well be caused by a more active immune system but what is the primary cause? Are we to blame the artherial repair apparatus for stuffing too much "bandage" over an injured endothelium? Why was endothelium injured in the first place?

As one reads further into discussion section, it raises more questions. Even the authors themselves, seem to undermine their assumption that it is the increased leukotrienes production associated with TWO-5LOX genome that is causing 11% thicker IMT. They say that the TWO-5LOX genome may even downregulate leukotrienes production, or are not certain whether it down or up regulates it. If it doesn't then it makes AA irrelevant to the whole issue.

See this quote (page 36):

If the 5-lipoxygenase pathway in cells involved in atherosclerosis is down-regulated among carriers of two variant alleles, as suggested by the reduction in reporter construct activity in HeLa cells, then our observation of increased atherosclerosis among such subjects appears paradoxical.
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