Deftereos Spyridon, Angelidis Christos, Bouras Georgios, Raisakis Konstantinos, Gerckens Ulrich, Cleman Michael W, Giannopoulos Georgios
Department of Cardiology, Athens General Hospital "G. Gennimatas" Mesogeion 154, 11527, Athens, Greece.
Med Chem. 2014;10(7):653-62. doi: 10.2174/1573406410666140806103651.
The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing.
现代介入心脏病学的“圣杯”是挽救急性闭塞冠状动脉供血区域内的存活心肌组织。溶栓和经皮冠状动脉介入治疗，只要能及时实施，就能解除血管闭塞并挽救组织。与此同时，恢复冠状动脉通畅并为缺血心肌供血可能会导致额外的组织损伤。炎症反应是缺血再灌注损伤的关键因素，也是受损心肌损伤演变的主要决定因素。固有免疫系统启动并引导这种反应，而这是后续愈合的先决条件。补体级联反应在亚细胞膜成分释放后启动。从缺血和濒死细胞释放的内源性“危险”信号，即所谓的危险相关分子模式（DAMPs），会提醒固有免疫系统，并通过与高度保守的Toll样受体（TLRs）相互作用激活多种信号转导途径。活性氧（ROS）的产生直接诱导促炎级联反应并触发炎性小体的形成。挑战在于设计出能特异性阻断导致组织损伤的炎症级联反应而又不影响与组织愈合相关的炎症级联反应的策略。
