Toll-like receptors and atherosclerosis

Toll like receptors (TLR) are receptors with major role in activationof immune system by regulating production of chemokinesand cytokines, which makes them important in different types ofinflammatory reactions- bacterial, viral, parasitic, acute, chronicetc. Having in mind that atherosclerosis is a chronic inflammatorydisease, it is clear then that TLRs are a group of immune systemactivators, producing specific immune cells. In human atheroscleroticplaque there is a markedly enhanced expression of TLR1,TLR2, and TLR4. TLRs are expressed in adrenal cells, and TLRagonists stimulate the release of steroids from human adrenalgland, as well. TLR2 deficient mice have an impaired steroid releaseduring endotoxemia. TLR9 stimulation leads to a corticosteroneand inflammatory cytokine response. The best characterizedof all is TLR4. Up to date this TLR has a major role in thedevelopment of atherosclerosis. Enhanced expression of hTLR4(human TLR4) in patients with ACS (acute coronary syndrome)was associated with elevations of IL-12 and B7-1 expression, astypical downstream effects of TLR4 activation. It is known that acertain gene polymorphism of TLR4 can slow progression of thedisease. Over expression of TLR2 in mice facilitates ventricularremodeling after myocardial infarction. The CAPS study foundcontrary results, when in 3000 patients no connection had beenfound between TLR2 polymorphism (Arg 753 Gln,-16934A/T)and TLR4 polymorphism (D299G, T399I) and the process of atherosclerosis.