Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Cardiovasc Res. 2012 May 1;94(2):276-83. doi: 10.1093/cvr/cvs018. Epub 2012 Jan 20.
One of the major therapeutic challenges in the arena of interventional cardiology is to design strategies aimed at reducing myocardial tissue damage after myocardial infarction. In response to tissue injury, an innate immune response is initiated that orchestrates homeostatic responses and is a prerequisite for subsequent wound healing. An exaggerated inflammatory reaction, however, countervenes these beneficial effects and contributes to maladaptive tissue damage. Herein, we discuss the pathways involving the innate immune system that have been investigated in the setting of myocardial ischaemia and reperfusion injury. Endogenous 'danger' signals [danger-associated molecular patterns (DAMPs)] are expressed following tissue injury and alert the innate immune system. Toll-like receptors and the complement system are activated, resulting in an inflammatory reaction involving inflammatory cell influx and the production and release of inflammatory cytokines. A potential involvement of cell-derived microparticles in the modulation of the innate immune response following myocardial injury will also be discussed. Our future challenge lies within the counteraction of maladaptive inflammatory cascades, without interfering in the benign wound healing response, and in translating these anti-inflammatory strategies into clinical practice.
在介入心脏病学领域，主要的治疗挑战之一是设计旨在减少心肌梗死后心肌组织损伤的策略。针对组织损伤，会启动先天免疫反应，协调体内平衡反应，是随后伤口愈合的前提。然而，过度的炎症反应会抵消这些有益作用，并导致适应性组织损伤。在此，我们讨论了在心肌缺血再灌注损伤情况下研究过的涉及先天免疫系统的途径。组织损伤后会表达内源性“危险”信号（危险相关分子模式（DAMPs）），并向先天免疫系统发出警报。Toll 样受体和补体系统被激活，导致炎症细胞浸润以及炎症细胞因子的产生和释放的炎症反应。还将讨论细胞来源的微颗粒在心肌损伤后先天免疫反应调节中的潜在作用。我们未来的挑战在于对抗适应性炎症级联反应，而不干扰良性伤口愈合反应，并将这些抗炎策略转化为临床实践。
