University Hospital Würzburg, Department of Internal Medicine I, Oberdürrbacherstraße 6, 97080 Würzburg, Germany.
Expert Opin Ther Targets. 2011 Jun;15(6):753-65. doi: 10.1517/14728222.2011.566560. Epub 2011 Mar 9.
The innate immune system can detect the highly conserved, relatively invariant structural motifs of pathogens. The most important innate immune receptors, Toll-like receptors (TLRs), represent a first line of defense against infectious pathogens, and play a pivotal role in initiating and shaping innate and adaptive immune responses. TLRs are not only expressed in immune cells, but also in cardiovascular cells. In addition to their role in response to microbial infections, evidence suggests that TLRs can also recognize endogenous ligands and may play a role in mediating cardiomyocyte cell death and survival after non-infectious injury.
TLRs could be a link between cardiovascular diseases and the immune system. Experimentally, there is good evidence that TLR activation contributes to development and progression of both acute cardiac injury and chronic heart failure. The role of TLRs in myocardial ischemia-reperfusion, remodeling, septic cardiomyoparthy, autoimmune- and viral myocarditis, anthracycline-induced cardiomyopathy and cardiac hypertrophy, in basic as well as clinical science are discussed.
Evidence, mainly from animal experiments, indicates that TLRs contribute to all of the myocardial disease states reviewed in this paper. However, the relevance of TLRs as therapeutic targets remains to be defined as clinical data is sparse.
先天免疫系统可以识别病原体高度保守且相对不变的结构基序。最重要的先天免疫受体 Toll 样受体(TLR)是抵御感染性病原体的第一道防线,在启动和塑造先天和适应性免疫反应方面发挥着关键作用。TLR 不仅在免疫细胞中表达,也在心血管细胞中表达。除了在应对微生物感染中的作用外,有证据表明 TLR 还可以识别内源性配体,并可能在介导非传染性损伤后心肌细胞死亡和存活中发挥作用。
TLR 可能是心血管疾病和免疫系统之间的联系。实验证据表明,TLR 激活有助于急性心脏损伤和慢性心力衰竭的发展和进展。讨论了 TLR 在心肌缺血再灌注、重塑、脓毒症性心肌病、自身免疫性和病毒性心肌炎、蒽环类药物诱导性心肌病和心肌肥厚中的作用,包括基础科学和临床科学。
主要来自动物实验的证据表明,TLR 参与了本文综述的所有心肌疾病状态。然而,作为治疗靶点的 TLR 的相关性仍有待确定,因为临床数据很少。