Pyridoxine, Collagen, and Vascular Remodeling

This article [Peeters et al., 2007: (http://www.ncbi.nlm.nih.gov/pubmed/17398378)] is interesting, and the authors found that low vitamin B6 (pyridoxine) status (plasma PLP) was associated with an increase in the risk of developing an abdominal aortic aneurysm (with an odds ratio of 3.75). The authors hypothesized that low pyridoxine intakes could reduce collagen biosynthesis in the wall of the aorta (in the outermost layer of the aorta, the adventitia, and presumably also in the media, the layer of smooth muscle cells and connective tissue beneath the endothelial cells of the intima). The authors noted that disturbances in collagen formation, in response to pyridoxine depletion, could impair the remodeling process in the aorta and lead to the development of aneurysms. The authors noted and cited references discussing the fact that lysyl oxidase activity is decreased in pyridoxine deficiency, and that's a copper-dependent enzyme. I think that enhancement of lysyl oxidase activity (one of the enzymes involved in collagen maturation) in response to pyridoxine repletion might be secondary, though, to pyridoxine-induced increases in ornithine delta-aminotransferase (OAT) activity [Inubushi et al., 2005: (http://www.ncbi.nlm.nih.gov/pubmed/16179747)]. Inubushi et al. (2005) found evidence that the decrease in collagen biosynthesis that occurs in response to pyridoxine depletion is the result of a reduction in the OAT-mediated conversion of ornithine into proline, via an intervening step. Proline is a major constituent of collagen. There might be some secondary mechanism by which proline availability enhances the expression of lysyl oxidase, etc. This type of thing might be relevant to the prevention of hemorrhages, given that some researchers have suggested the association between severe iron deficiency and hemorrhage might be due to reductions, produced by iron deficiency, in the iron-dependent lysyl and prolyl hydroxylase enzymes. Those are involved in collagen formation and other processes. An excess of iron would be damaging to blood vessels, though.

It's worth noting that only tiny amounts of copper are needed for lysyl oxidase activity, and supplementing copper past some miniscule level, of 500 mcg or less or something like that, so that one's intake from that and from food would reach the RDA of 0.9-1.2 mg or whatever, seems like not a good idea to me. Excess copper is transported by albumin and not by ceruloplasmin, and that sounds really bad to me. The binding of zinc and other metals to albumin and plasma proteins is really dynamic and unstable and can be disrupted by free fatty acids and many other factors. And tiny elevations in intracellular copper have been shown to cause extreme oxidative damage. Supposedly the intracellular, non-protein-bound copper is kept almost undetectably-low, but then why on Earth is a "spillover" fraction of dietary copper transported by albumin (if the transport mechanisms are so sophisticated and infallible)? I guess no one can answer that, but that's my point.