Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Research, G.V. (Sonny) Montgomery VA Medical Center, Jackson, Mississippi, USA.
FASEB J. 2024 Oct 31;38(20):e70106. doi: 10.1096/fj.202401404R.
Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Metabolic imbalances and pathological stress often contribute to increased mortality. Sestrin2 (Sesn2) is a stress-inducible protein crucial in maintaining cardiac energy and metabolic homeostasis under pathological conditions. Sesn2 is upregulated in response to various stressors, including oxidative stress, hypoxia, and energy depletion, and mediates multiple cellular pathways to enhance antioxidant defenses, promote autophagy, and inhibit inflammation. This review explores the mechanisms through which Sesn2 regulates these pathways, focusing on the AMPK-mTORC1, Sesn2-Nrf2, and HIF1α-Sesn2 pathways, among others. We can identify the potential therapeutic targets for treating CVDs and related metabolic disorders by comprehending these complex mechanisms. Sesn2's unique ability to respond thoroughly to metabolic challenges, oxidative stress, and inflammation makes it a promising prospect for enhancing cardiac health and resilience against pathological stress.
心血管疾病（CVDs）是全球发病率和死亡率的主要原因。代谢失衡和病理应激常常导致死亡率增加。Sesn2（Sesn2）是一种应激诱导蛋白，在病理条件下对于维持心脏能量和代谢稳态至关重要。Sesn2 可响应多种应激原（包括氧化应激、缺氧和能量耗竭）而上调，并通过多种细胞途径介导，增强抗氧化防御、促进自噬和抑制炎症。本综述探讨了 Sesn2 调节这些途径的机制，重点介绍了 AMPK-mTORC1、Sesn2-Nrf2 和 HIF1α-Sesn2 等途径。通过理解这些复杂的机制，我们可以确定治疗 CVDs 和相关代谢紊乱的潜在治疗靶点。Sesn2 能够全面应对代谢挑战、氧化应激和炎症的独特能力使其成为增强心脏健康和抵御病理应激能力的有希望的前景。
