Yamamoto Koji, Takeshita Kyosuke, Kojima Tetsuhito, Takamatsu Junki, Saito Hidehiko
Department of Transfusion Medicine, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
Cardiovasc Res. 2005 May 1;66(2):276-85. doi: 10.1016/j.cardiores.2004.11.013. Epub 2004 Dec 8.
Thrombotic cardiovascular diseases increase in incidence in the elderly, a tendency dependent on the age-related changes in vascular and hemostatic systems that include platelets, coagulation, and fibrinolytic factors as well as in the endothelium. The hypercoagulability of and advanced sclerotic changes in the vascular wall may contribute to the increased incidence of thrombosis in the elderly. One of the important key genes for aging-associated thrombosis is plasminogen activator inhibitor-1 (PAI-1), a principal inhibitor of fibrinolysis. The expression of PAI-1 is not only elevated in the elderly but also significantly induced in a variety of pathologies associated with the process of aging. These conditions include obesity, insulin resistance, emotional stress, immune responses, and vascular sclerosis/remodeling. Several cytokines and hormones, including tumor necrosis factor-alpha, transforming growth factor-beta, angiotensin II, and insulin, positively regulate the gene expression of PAI-1. The recent epidemic in obesity with aging in the industrialized society may heighten the risk for thrombotic cardiovascular disease because adipose tissue is a primary source of PAI-1 and cytokines. Emotional or psychosocial stress and inflammation also cause the elevated expression of PAI-1 in an age-specific pattern. Thus, PAI-1 could play a key role in the progression of cardiovascular aging by promoting thrombosis and vascular (athero)sclerosis. Further studies on the genetic mechanism of aging-associated PAI-1 induction will be necessary to define the basis for cardiovascular aging in relation to thrombosis.
血栓性心血管疾病的发病率在老年人中呈上升趋势，这种趋势取决于血管和止血系统中与年龄相关的变化，这些系统包括血小板、凝血因子、纤维蛋白溶解因子以及内皮细胞。血管壁的高凝性和晚期硬化改变可能导致老年人血栓形成的发病率增加。与衰老相关血栓形成的重要关键基因之一是纤溶酶原激活物抑制剂-1（PAI-1），它是纤维蛋白溶解的主要抑制剂。PAI-1的表达不仅在老年人中升高，而且在与衰老过程相关的各种病理状态下也会显著诱导。这些情况包括肥胖、胰岛素抵抗、情绪应激、免疫反应以及血管硬化/重塑。几种细胞因子和激素，包括肿瘤坏死因子-α、转化生长因子-β、血管紧张素II和胰岛素，正向调节PAI-1的基因表达。在工业化社会中，随着年龄增长肥胖症的流行可能会增加血栓性心血管疾病的风险，因为脂肪组织是PAI-1和细胞因子的主要来源。情绪或心理社会应激以及炎症也会以年龄特异性模式导致PAI-1表达升高。因此，PAI-1可能通过促进血栓形成和血管（动脉粥样）硬化在心血管衰老进程中发挥关键作用。有必要对衰老相关的PAI-1诱导的遗传机制进行进一步研究，以确定与血栓形成相关的心血管衰老的基础。
