Toll-like receptors and atherosclerosis

Toll like receptors (TLR) are receptors with major role in activation of immune system by regulating production of chemokines and cytokines, which makes them important in different types of inflammatory reactions- bacterial, viral, parasitic, acute, chronic etc. Having in mind that atherosclerosis is a chronic inflammatory disease, it is clear then that TLRs are a group of immune system activators, producing specific immune cells. In human atherosclerotic plaque there is a markedly enhanced expression of TLR1, TLR2, and TLR4. TLRs are expressed in adrenal cells, and TLR agonists stimulate the release of steroids from human adrenal gland, as well. TLR2 deficient mice have an impaired steroid release during endotoxemia. TLR9 stimulation leads to a corticosterone and inflammatory cytokine response. The best characterized of all is TLR4. Up to date this TLR has a major role in the development 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, as typical downstream effects of TLR4 activation. It is known that a certain gene polymorphism of TLR4 can slow progression of the disease. Over expression of TLR2 in mice facilitates ventricular remodeling after myocardial infarction. The CAPS study found contrary results, when in 3000 patients no connection had been found between TLR2 polymorphism (Arg 753 Gln,-16934A/T) and TLR4 polymorphism (D299G, T3991) and the process of atherosclerosis.