A clear hypoth esis is emerging in which chronic infection inflammation in the vasculature leads, in the short term, to blockade of pathogen proliferation but in the longer term to 25OHC driven fatty droplet accumulation and vascular occlusion. Is a battle being played out www.selleckchem.com/products/Lenalidomide.html in our vasculature, where the accumulation of cholesteryl esters, precipitat ing ATH or AD, is the price of surviving the onslaught of an invading pathogen Selective inhibitors of CH25H and or ACAT may therefore have clinical potential in both diseases, indeed, some widely available dietary components are under investigation as possible protective agents. Conversely, preventive mea sures against pathogen infection are unlikely to be productive, not only because of the diversity of potentially causal agents but also because, for several pathogens, a substantial proportion of the population is already positive from childhood onwards.

Inhibitors,Modulators,Libraries In addition, remarkably, in some cases early infection could even be beneficial. Barnton et al. report that latent infection of mice with herpes viruses confers resistance to bacterial infection, with a 100 1000 fold reduction in the replication of Listeria monocytogenes or Yersinia pestis. Resistance was not antigen specific, and required chronic IFN production, suggesting that similar pathways may be exploited by latent viruses providing a first indication that bifurcation of immunosterol pathways might potentially foster one pathogen at the expense of another. The striking age dependence of disease is not under stood.

For many pathogens, infections are acquired in early childhood Inhibitors,Modulators,Libraries and remain stable, but for others there is a clear age related increase in seropositivity rates. A Inhibitors,Modulators,Libraries recent exciting development is that macro phages show an age related decline in the expression of the key cholesterol efflux protein, Inhibitors,Modulators,Libraries ABCA1, impli cated in both ATH and AD. However, Inhibitors,Modulators,Libraries given that age related phenomena are con trolled systemically rather than being cell intrinsic, a more attractive hypothesis might be that the well documented lifetime declines in tissue levels of steroidal molecules such as 7 dehydrocholesterol, allopregnenolone, and dehydroepiandrosterone, that interact with the self same sterol pathways discussed here, contrib ute to disease processes. Indeed, protective effects of vitamin D and DHEA in both ATH and AD models have been reported, lifetime changes in androgens and estrogens may also play a role.

Ill or just old This debate has highlighted many lines of evidence that two major age related diseases are likely to be precipi tated by infection and inflammation, and are not merely a consequence check details of age per se. However in the terms of Izaks and Westendorp infection inflammation is a component cause, but not a sufficient cause. There are undoubtedly good reasons to suspect that a systemic age related component so far unidentified contributes to both diseases.