背景:动脉粥样硬化(AS)是一种进行性疾病,会干扰血流,导致心血管并发症,如高血压,缺血性心脏病,缺血性卒中,和血管缺血。AS的进展与炎症相关,氧化应激,和内皮功能障碍。各种信号通路,如核红系相关因子2(Nrf2)和Kruppel样因子2(KLF2),参与AS的发病机制。Nrf2和KLF2具有抗炎和抗氧化特性。因此,这些途径的激活可能会减少AS的发展。二甲双胍,一种用于2型糖尿病(T2DM)管理的胰岛素增敏药物,增加Nrf2和KLF2的表达。AS是T2DM常见的长期大血管并发症。因此,二甲双胍,通过其多效抗炎作用,可能减弱AS的发展和进展。
目标:因此,本文旨在探讨二甲双胍对Nrf2和KLF2的影响以及抑制活性氧(ROS)形成在AS中的可能作用。除了其抗糖尿病作用,与其他抗糖尿病药物相比,二甲双胍可以降低心血管发病率和死亡率,即使与Nrf2/KLF2途径激活的血糖控制相似。
结论:结论:二甲双胍是对抗AS发展和进展的有效治疗策略,主要通过激活KLF2/Nrf2轴。
BACKGROUND: Atherosclerosis (AS) is a progressive disease that interferes with blood flow, leading to cardiovascular complications such as hypertension, ischemic heart disease, ischemic stroke, and vascular ischemia. The progression of AS is correlated with inflammation, oxidative stress, and endothelial dysfunction. Various signaling pathways, like nuclear erythroid-related factor 2 (Nrf2) and Kruppel-like factor 2 (KLF2), are involved in the pathogenesis of AS. Nrf2 and KLF2 have anti-inflammatory and antioxidant properties. Thus, activation of these pathways may reduce the development of AS. Metformin, an insulin-sensitizing drug used in the management of type 2 diabetes mellitus (T2DM), increases the expression of Nrf2 and KLF2. AS is a common long-term macrovascular complication of T2DM. Thus, metformin, through its pleiotropic anti-inflammatory effect, may attenuate the development and progression of AS.
OBJECTIVE: Therefore, this review aims to investigate the possible role of metformin in AS concerning its effect on Nrf2 and KLF2 and inhibition of reactive oxygen species (ROS) formation. In addition to its antidiabetic effect, metformin can reduce cardiovascular morbidities and mortalities compared to other antidiabetic agents, even with similar blood glucose control by the Nrf2/KLF2 pathway activation.
CONCLUSIONS: In conclusion, metformin is an effective therapeutic strategy against the development and progression of AS, mainly through activation of the KLF2/Nrf2 axis.