Oude Nijhuis M M, van Keulen J K, Pasterkamp G, Quax P H, de Kleijn D P V
Experimental Cardiology Laboratory, Heart Lung Center Utrecht, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Curr Pharm Des. 2007;13(10):983-94. doi: 10.2174/138161207780487593.
Innate immunity is the first line of defence against invading micro-organisms. The family of Toll-like receptors (TLRs) recognizes pathogen-associated molecular patterns (PAMPs) that are carried by the invading micro-organisms. Infectious pathogens have been implicated to play an important role in atherosclerosis. Nowadays, evidence is accumulating that TLRs play an important role in the initiation and progression of atherosclerosis too. A lot is known about the exogenous ligands that are able to activate the TLRs, but it is also known that endogenous ligands have the capacity to activate TLRs when exogenous ligands are absent. Studies on knockout mice, epidemiological studies and even human polymorphism studies confirmed the important role of TLRs in development and progression of atherosclerotic disease. Studies with antagonists against TLR ligands and vaccination studies demonstrated that TLR signaling might be a potential target for intervention in the initiation and progression of atherosclerosis.
固有免疫是抵御入侵微生物的第一道防线。Toll样受体(TLR)家族可识别入侵微生物携带的病原体相关分子模式(PAMP)。传染性病原体被认为在动脉粥样硬化中起重要作用。如今,越来越多的证据表明TLR在动脉粥样硬化的发生和发展中也起重要作用。关于能够激活TLR的外源性配体我们了解很多,但也知道在内源性配体不存在时,内源性配体也有激活TLR的能力。对基因敲除小鼠的研究、流行病学研究甚至人类多态性研究都证实了TLR在动脉粥样硬化疾病发生和发展中的重要作用。使用TLR配体拮抗剂的研究和疫苗接种研究表明,TLR信号传导可能是干预动脉粥样硬化发生和发展的一个潜在靶点。