Endothelial senescence is the main risk factor that contributes to vascular dysfunction and the progression of vascular disease. Carbon monoxide (CO) plays an important role in preventing vascular dysfunction and in maintaining vascular physiology or homeostasis. The application of exogenous CO has been shown to confer protection in several models of cardiovascular injury or disease, including hypertension, atherosclerosis, balloon-catheter injury, and graft rejection. However, the mechanism by which CO prevents endothelial senescence has been largely unexplored. The aim of this study was to evaluate the effects of CO on endothelial senescence and to investigate the possible mechanisms underlying this process. We measured the levels of senescence-associated-β-galactosidase activity, senescence-associated secretory phenotype, reactive oxygen species (ROS) production, and stress granule in human umbilical vein endothelial cells and the WI-38 human diploid fibroblast cell line. We found that 5-fluorouracil (5FU)-induced ROS generation was inhibited by CO-releasing molecules (CORM)-A1 treatment, and endothelial senescence induced by 5FU was attenuated by CORM-A1 treatment. The SIRT1 inhibitor EX527 reversed the inhibitory effect of CO on the 5FU-induced endothelial senescence. Furthermore, SIRT1 deficiency abolished the stress granule formation by CO. Our results suggest that CO alleviates the endothelial senescence induced by 5FU through SIRT1 activation and may hence have therapeutic potential for the treatment of vascular diseases.

内皮衰老是导致血管功能障碍和血管疾病进展的主要危险因素。一氧化碳（CO）在预防血管功能障碍和维持血管生理或体内平衡方面起着重要作用。已显示外源性CO的应用可在多种心血管损伤或疾病模型中提供保护，包括高血压，动脉粥样硬化，球囊导管损伤和移植物排斥。然而，CO阻止内皮细胞衰老的机制尚未被广泛探索。这项研究的目的是评估一氧化碳对内皮细胞衰老的影响，并研究这一过程的潜在机制。我们测量了衰老相关的β-半乳糖苷酶活性，衰老相关的分泌表型，人脐静脉内皮细胞和WI-38人二倍体成纤维细胞系中活性氧（ROS）的产生和应激颗粒。我们发现5-氟尿嘧啶（5FU）诱导的ROS生成被CO释放分子（CORM）-A1处理抑制，而5FU诱导的内皮衰老被CORM-A1处理减弱。SIRT1抑制剂EX527逆转了CO对5FU诱导的内皮细胞衰老的抑制作用。此外，SIRT1缺乏消除了CO引起的应激颗粒形成。我们的结果表明，CO通过SIRT1激活减轻了5FU诱导的内皮衰老，因此可能具有治疗血管疾病的潜力。我们发现5-氟尿嘧啶（5FU）诱导的ROS生成被CO释放分子（CORM）-A1处理抑制，而5FU诱导的内皮衰老被CORM-A1处理减弱。SIRT1抑制剂EX527逆转了CO对5FU诱导的内皮细胞衰老的抑制作用。此外，SIRT1缺乏消除了CO引起的应激颗粒形成。我们的结果表明，CO通过SIRT1激活减轻了5FU诱导的内皮衰老，因此可能具有治疗血管疾病的潜力。我们发现5-氟尿嘧啶（5FU）诱导的ROS生成被CO释放分子（CORM）-A1处理抑制，而5FU诱导的内皮衰老被CORM-A1处理减弱。SIRT1抑制剂EX527逆转了CO对5FU诱导的内皮细胞衰老的抑制作用。此外，SIRT1缺乏消除了CO引起的应激颗粒形成。我们的结果表明，CO通过SIRT1激活减轻了5FU诱导的内皮衰老，因此可能具有治疗血管疾病的潜力。