Valantine Hannah A
Falk Cardiovascular Research Center, Stanford University, California 94305-5406, USA.
Transplantation. 2003 Sep 27;76(6):891-9. doi: 10.1097/01.TP.0000080981.90718.EB.
Endothelial injury plays a central role in the pathophysiologic mechanisms underlying cardiac allograft vasculopathy (CAV). Although the accelerated course of CAV and its localization to the allograft support an important role for the alloimmune response, there is considerable evidence implicating lipoprotein abnormalities, metabolic disturbances, viral infections, and systemic inflammation in the process. This multifactorial basis for CAV may be put into a pathophysiologic context in which endothelial cell injury is the triggering event that initiates and drives the proliferative and fibrotic processes characteristic of CAV. In the transplant setting, endothelial cell injury is induced by multiple factors, including brain death, ischemia-reperfusion, alloimmune responses, and viral infections. Once initiated, propagation of the proliferative processes that ultimately lead to vascular occlusion is enhanced by the abnormal metabolic environment of elevated lipoproteins and insulin resistance encountered in most patients. This review examines the evidence for the role of potential triggers of endothelial injury in the pathophysiology of CAV and discusses the central role of the nitric oxide pathway in the disease process.
内皮损伤在心脏移植血管病变（CAV）的病理生理机制中起核心作用。尽管CAV的加速病程及其在移植心脏中的定位表明同种异体免疫反应起重要作用，但有大量证据表明脂蛋白异常、代谢紊乱、病毒感染和全身炎症在此过程中也有牵连。CAV的这种多因素基础可能被置于一种病理生理背景中，其中内皮细胞损伤是引发并驱动CAV特征性增殖和纤维化过程的触发事件。在移植环境中，内皮细胞损伤由多种因素诱导，包括脑死亡、缺血再灌注、同种异体免疫反应和病毒感染。一旦启动，大多数患者所遇到的脂蛋白升高和胰岛素抵抗的异常代谢环境会增强最终导致血管闭塞的增殖过程的传播。本综述探讨了内皮损伤潜在触发因素在CAV病理生理学中作用的证据，并讨论了一氧化氮途径在疾病过程中的核心作用。
