Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Life Sci. 2023 Oct 1;330:122007. doi: 10.1016/j.lfs.2023.122007. Epub 2023 Aug 5.
Coronary artery disease (CAD) is the leading cause of death worldwide. Oxidative stress and inflammation are major mechanisms responsible for the progression of CAD. Nuclear transcription factor erythroid-2 related factor 2 (Nrf2) is a transcription factor that modulates the cellular redox status. Nrf2 upregulation increases the expression of antioxidant genes, decreases the expression of Nuclear factor-kappa B (NF-kB), and increases free radical metabolism. Activated NF-kB increases the production of inflammatory cytokines causing endothelial dysfunction. The two pathways of Nrf2 and NF-kB can regulate the expression of each other. Foremost, the Nrf2 pathway can decrease the level of active NF-κB by increasing the level of antioxidants and cytoprotective enzymes. Furthermore, the Nrf2 pathway prevents IκB-α degradation, an inhibitor of NF-kB, and thus inhibits NF-κB mediated transcription. Also, NF-kB transcription inhibits Nrf2 activation by reducing the antioxidant response element (ARE) transcription. Sirtuin 6 (SIRT6) is a member of the Sirtuins family that was found to protect against cardiovascular diseases. SIRT6 can suppress the production of Reactive oxygen species (ROS) through deacetylation of NRF2 which results in NRF2 activation. Furthermore, SIRT6 can inhibit the inflammatory process through the downregulation of NF-kB transcription. Therefore, targeting sirtuins could be a therapeutic strategy to treat CAD. This review describes the potential role of SIRT6 in regulating the crosstalk between NRF2 and NF-kB signaling pathways in CAD.
冠心病（CAD）是全球范围内的主要死亡原因。氧化应激和炎症是导致 CAD 进展的主要机制。核转录因子红细胞 2 相关因子 2（Nrf2）是一种调节细胞氧化还原状态的转录因子。Nrf2 的上调增加了抗氧化基因的表达，降低了核因子-κB（NF-κB）的表达，并增加了自由基代谢。激活的 NF-κB 增加了炎症细胞因子的产生，导致内皮功能障碍。Nrf2 和 NF-κB 的两条途径可以相互调节彼此的表达。首先，Nrf2 途径可以通过增加抗氧化剂和细胞保护酶的水平来降低活性 NF-κB 的水平。此外，Nrf2 途径通过防止 NF-κB 介导的转录来抑制 IκB-α 的降解，IκB-α 是 NF-κB 的抑制剂。此外，NF-κB 转录通过减少抗氧化反应元件（ARE）转录来抑制 Nrf2 激活。Sirtuin 6（SIRT6）是 Sirtuins 家族的一员，被发现可以预防心血管疾病。SIRT6 通过去乙酰化 NRF2 抑制活性氧（ROS）的产生，从而导致 NRF2 激活。此外，SIRT6 可以通过抑制 NF-κB 转录来抑制炎症过程。因此，靶向 Sirtuins 可能是治疗 CAD 的一种治疗策略。本综述描述了 SIRT6 在调节 CAD 中 NRF2 和 NF-κB 信号通路相互作用中的潜在作用。
