Yang Hong, Shi MingJian, Story James, Richardson Arlan, Guo ZhongMao
Department of Physiology, Meharry Medical College, Nashville, Tennessee 37208, USA.
J Gerontol A Biol Sci Med Sci. 2004 Apr;59(4):316-23. doi: 10.1093/gerona/59.4.b316.
Age-related endothelial dysfunction has been suggested to play a role in atherogenesis. Food restriction (FR) has been shown to retard the development of atherosclerosis. The goal of this report is to assess the effect of aging and FR on endothelial functions, including the release of endothelial nitric oxide (NO) and the adhesion of mononuclear cells (MNCs) to endothelial cells (ECs). ECs were obtained from the aorta of young mice fed ad libitum (Y-AL), old mice fed ad libitum (O-AL), or a food-restricted diet (O-FR). When compared with those obtained from Y-AL and O-FR mice, ECs obtained from O-AL mice decreased the basal level of NO release and increased the basal level of peroxynitrite, superoxide, and hydrogen peroxide. In addition, ECs obtained from O-AL elevated the response to CuSO4-oxidized low-density lipoprotein (oxLDL). For example, incubation with oxLDL reduced NO release approximately 52% in ECs obtained from O-AL mice. In contrast, the same dose of oxLDL reduced NO release only approximately 40% in ECs obtained from Y-AL and O-FR mice. Moreover, the level of oxLDL-induced adhesion of MNCs and oxLDL-induced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 was markedly higher in ECs obtained from O-AL mice as compared with those obtained from Y-AL and O-FR mice. These results suggest that aging increases the sensitivity of ECs in response to oxLDL-reduced endothelial NO release and oxLDL-increased adhesion of MNCs to ECs. FR attenuates age-related increase in the sensitivity of ECs to oxLDL, which might be responsible, at least in part, for the antiatherogenic action of FR.
年龄相关的内皮功能障碍被认为在动脉粥样硬化的发生发展中起作用。食物限制（FR）已被证明可延缓动脉粥样硬化的发展。本报告的目的是评估衰老和FR对内皮功能的影响，包括内皮一氧化氮（NO）的释放以及单核细胞（MNCs）与内皮细胞（ECs）的黏附。ECs取自自由进食的年轻小鼠（Y-AL）、自由进食的老年小鼠（O-AL）或接受食物限制饮食的老年小鼠（O-FR）。与从Y-AL和O-FR小鼠获得的ECs相比，从O-AL小鼠获得的ECs降低了NO释放的基础水平，并增加了过氧亚硝酸盐、超氧化物和过氧化氢的基础水平。此外，从O-AL获得的ECs增强了对硫酸铜氧化的低密度脂蛋白（oxLDL）的反应。例如，用oxLDL孵育使从O-AL小鼠获得的ECs中的NO释放减少约52%。相比之下，相同剂量的oxLDL仅使从Y-AL和O-FR小鼠获得的ECs中的NO释放减少约40%。此外，与从Y-AL和O-FR小鼠获得的ECs相比，从O-AL小鼠获得的ECs中oxLDL诱导的MNCs黏附水平以及oxLDL诱导的血管细胞黏附分子-1和细胞间黏附分子-1的表达明显更高。这些结果表明，衰老增加了ECs对oxLDL降低内皮NO释放和oxLDL增加MNCs与ECs黏附的敏感性。FR减弱了与年龄相关的ECs对oxLDL敏感性的增加，这可能至少部分地解释了FR的抗动脉粥样硬化作用。
