Rubanyi G M
Berlex Biosciences, Richmond, California 94804.
J Cardiovasc Pharmacol. 1993;22 Suppl 4:S1-14. doi: 10.1097/00005344-199322004-00002.
Key discoveries in the past decade have revealed that the vascular endothelium is an important regulatory organ that is involved in maintaining cardiovascular homeostasis in health and contributes significantly to the pathomechanism of several cardiovascular diseases. Occupying a strategically important location between circulating blood and tissues and having the ability to respond to changes in its physical, chemical, and humoral environment by the production of a host of biologically active substances, the normal endothelium modulates the tone of underlying vascular smooth muscle, maintains a nonadhesive luminal surface, and mediates hemostasis, cellular proliferation, and inflammatory and immune mechanisms in the vascular wall. Modulation of smooth-muscle tone is mediated by the synthesis release of endothelium-derived relaxing [PGI2, EDRF(NO), and EDHF] and contracting factors (arachidonic acid metabolites, endothelin-1, and angiotensin II). Anticoagulant, fibrinolytic, and antithrombotic properties contribute to the maintenance of the fluidity of blood. Injury or activation (by cytokines) of endothelial cells disrupts these normal regulatory mechanisms and results in morphologic and functional alterations (phenotypic changes) commonly defined as endothelial dysfunction. Clinically, the "syndrome" of endothelial cell dysfunction can be described as generalized or localized vasospasm, thrombosis, atherosclerosis, and restenosis. Although its importance is clearly established, no drugs used today were originally targeted for the treatment of endothelial dysfunction. Recent studies, however, showed that some existing therapies (e.g., angiotensin-converting enzyme inhibitors) may protect the endothelium. Novel diagnostic techniques and innovative therapeutic strategies, based on the already known molecular mechanisms of endothelial dysfunction, are briefly outlined. Further knowledge of the pathobiology of the impaired endothelium will contribute to unraveling some of the remaining mysteries of many cardiovascular diseases and will enable us to design novel therapies to prevent and treat them.
过去十年中的重要发现表明，血管内皮是一个重要的调节器官，它参与维持健康状态下的心血管稳态，并在多种心血管疾病的发病机制中发挥重要作用。正常内皮细胞位于循环血液与组织之间的战略要地，能够通过产生多种生物活性物质来响应其物理、化学和体液环境的变化，调节其下方血管平滑肌的张力，维持非黏附性的管腔表面，并介导止血、细胞增殖以及血管壁中的炎症和免疫机制。平滑肌张力的调节是由内皮源性舒张因子[前列环素2、内皮源性舒张因子（一氧化氮）和内皮源性超极化因子]和收缩因子（花生四烯酸代谢产物、内皮素-1和血管紧张素II）的合成与释放介导的。抗凝、纤维蛋白溶解和抗血栓形成特性有助于维持血液的流动性。内皮细胞的损伤或（由细胞因子引起的）激活会破坏这些正常调节机制，导致通常被定义为内皮功能障碍的形态和功能改变（表型变化）。临床上，内皮细胞功能障碍的“综合征”可表现为全身性或局部性血管痉挛、血栓形成、动脉粥样硬化和再狭窄。尽管其重要性已明确确立，但目前使用的药物最初均未针对内皮功能障碍进行治疗。然而，最近的研究表明，一些现有疗法（如血管紧张素转换酶抑制剂）可能对内皮具有保护作用。基于已知的内皮功能障碍分子机制，简要概述了新型诊断技术和创新治疗策略。对受损内皮病理生物学的进一步了解将有助于揭开许多心血管疾病的一些未解之谜，并使我们能够设计出预防和治疗这些疾病的新疗法。
