Hernández-Reséndiz Sauri, Muñoz-Vega Mónica, Contreras Whendy E, Crespo-Avilan Gustavo E, Rodriguez-Montesinos Julian, Arias-Carrión Oscar, Pérez-Méndez Oscar, Boisvert William A, Preissner Klaus T, Cabrera-Fuentes Hector A
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore.
National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
Cond Med. 2018 Aug;1(5):247-258.
One of the primary therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial infarct size and optimizing cardiac function following acute myocardial infarction (AMI). Patients with AMI who underwent reperfusion therapy display dysfunction of the coronary endothelium. Consequently, ischemic endothelial cells become more permeable and weaken their natural anti-thrombotic and anti-inflammatory potential. Ischemia-reperfusion injury (IRI) is associated with activation of the humoral and cellular components of the hemostatic and innate immune system, and also with excessive production of reactive oxygen species (ROS), the inhibition of nitric oxide synthase, and with inflammatory processes. Given its essential role in the regulation of vascular homeostasis, involving platelets and leukocytes among others, dysfunctional endothelium can lead to increased risk of coronary vasospasm and thrombosis. Endothelial dysfunction can be prevented by ischemic conditioning with a protective intervention based on limited intermittent periods of ischemia and reperfusion. The molecular mechanisms and signal transduction pathways underlying conditioning phenomena in the coronary endothelium have been described as involving less ROS production, reduced adhesion of neutrophils to endothelial cells and diminished inflammatory reactions. This review summarizes our current understanding of the cellular and molecular mechanisms regulating IRI-affected and -damaged coronary endothelium, and how ischemic conditioning may preserve its function.
现代心脏病学的主要治疗目标之一是制定策略，旨在使急性心肌梗死（AMI）后的心肌梗死面积最小化，并优化心脏功能。接受再灌注治疗的AMI患者表现出冠状动脉内皮功能障碍。因此，缺血的内皮细胞变得更具渗透性，并削弱其天然的抗血栓形成和抗炎潜力。缺血再灌注损伤（IRI）与止血和固有免疫系统的体液和细胞成分激活有关，还与活性氧（ROS）的过度产生、一氧化氮合酶的抑制以及炎症过程有关。鉴于其在调节血管稳态中的重要作用，包括血小板和白细胞等，功能失调的内皮可导致冠状动脉痉挛和血栓形成风险增加。内皮功能障碍可通过基于有限间歇性缺血和再灌注的保护性干预进行缺血预处理来预防。冠状动脉内皮预处理现象背后的分子机制和信号转导途径已被描述为涉及较少的ROS产生、中性粒细胞与内皮细胞的粘附减少以及炎症反应减弱。本综述总结了我们目前对调节受IRI影响和损伤的冠状动脉内皮的细胞和分子机制的理解，以及缺血预处理如何保护其功能。
