Department of Medicine, University of Vermont College of Medicine, Burlington, 05405, USA.
Antioxid Redox Signal. 2010 Mar 1;12(5):641-55. doi: 10.1089/ars.2009.2854.
Epidemiological studies have shown that advancing age is associated with an increased prevalence of cardiovascular disease (CVD). Vascular smooth muscle cells (VSMC) comprise the major arterial cell population, and changes in VSMC behavior, function, and redox status with age contribute to alterations in vascular remodeling and cell signaling. Over two decades of work on aged animal models provide support for age-related changes in VSMC and/or arterial tissues. Enhanced production of reactive oxygen species (ROS) and insufficient removal by scavenging systems are hallmarks of vascular aging. VSMC proliferation and migration are core processes in vascular remodeling and influenced by growth factors and signaling networks. The intrinsic link between gene regulation and aging often relates directly to transcription factors and their regulatory actions. Modulation of growth factor signaling leads to up- or downregulation of transcription factors that control expression of genes associated with VSMC proliferation, inflammation, and ROS production. Four major signaling pathways related to the transcription factors, AP-1, NF-kappaB, FoxO, and Nrf2, will be reviewed. Knowledge of age-related changes in signaling pathways in VSMC that lead to alterations in cell behavior and function consistent with disease progression may help in efforts to attenuate age-related CVD, such as atherosclerosis.
流行病学研究表明，年龄增长与心血管疾病（CVD）的患病率增加有关。血管平滑肌细胞（VSMC）构成了主要的动脉细胞群体，随着年龄的增长，VSMC 行为、功能和氧化还原状态的变化导致血管重塑和细胞信号的改变。二十多年来对老年动物模型的研究为 VSMC 和/或动脉组织的年龄相关性变化提供了支持。活性氧（ROS）的产生增强和清除系统的清除不足是血管老化的标志。VSMC 的增殖和迁移是血管重塑的核心过程，受生长因子和信号网络的影响。基因调控和衰老之间的内在联系通常直接与转录因子及其调节作用有关。生长因子信号的调节导致控制与 VSMC 增殖、炎症和 ROS 产生相关基因表达的转录因子的上调或下调。将对与转录因子相关的四个主要信号通路（AP-1、NF-κB、FoxO 和 Nrf2）进行综述。了解 VSMC 中导致细胞行为和功能改变的信号通路的年龄相关性变化，这些改变与疾病进展一致，可能有助于减轻与年龄相关的 CVD，如动脉粥样硬化。
