Cellular and Molecular Cardiovascular Pathophysiology Laboratory, Department of Biology, Ecology and Earth Sciences (DiBEST), University of Calabria, Rende, Italy.
National Institute of Cardiovascular Research (INRC), Bologna, Italy.
Antioxid Redox Signal. 2024 Mar;40(7-9):369-432. doi: 10.1089/ars.2023.0285.
Physiological levels of reactive oxygen and nitrogen species (ROS/RNS) function as fundamental messengers for many cellular and developmental processes in the cardiovascular system. ROS/RNS involved in cardiac redox-signaling originate from diverse sources, and their levels are tightly controlled by key endogenous antioxidant systems that counteract their accumulation. However, dysregulated redox-stress resulting from inefficient removal of ROS/RNS leads to inflammation, mitochondrial dysfunction, and cell death, contributing to the development and progression of cardiovascular disease (CVD). Basic and clinical studies demonstrate the critical role of selenium (Se) and selenoproteins (unique proteins that incorporate Se into their active site in the form of the 21 proteinogenic amino acid selenocysteine [Sec]), including glutathione peroxidase and thioredoxin reductase, in cardiovascular redox homeostasis, representing a first-line enzymatic antioxidant defense of the heart. Increasing attention has been paid to emerging selenoproteins in the endoplasmic reticulum (ER) (, a multifunctional intracellular organelle whose disruption triggers cardiac inflammation and oxidative stress, leading to multiple CVD), which are crucially involved in redox balance, antioxidant activity, and calcium and ER homeostasis. This review focuses on endogenous antioxidant strategies with therapeutic potential, particularly selenoproteins, which are very promising but deserve more detailed and clinical studies. The importance of selective selenoproteins in embryonic development and the consequences of their mutations and inborn errors highlight the need to improve knowledge of their biological function in myocardial redox signaling. This could facilitate the development of personalized approaches for the diagnosis, prevention, and treatment of CVD. 40, 369-432.
生理水平的活性氧和氮物种 (ROS/RNS) 作为心血管系统中许多细胞和发育过程的基本信使。参与心脏氧化还原信号转导的 ROS/RNS 源自多种来源，其水平受到关键内源性抗氧化系统的严格控制，这些系统可对抗其积累。然而，由于 ROS/RNS 去除效率低下而导致的失调的氧化应激会导致炎症、线粒体功能障碍和细胞死亡，从而促进心血管疾病 (CVD) 的发展和进展。基础和临床研究表明，硒 (Se) 和硒蛋白（将 Se 以 21 种蛋白质氨基酸硒代半胱氨酸 [Sec] 的形式纳入其活性位点的独特蛋白质），包括谷胱甘肽过氧化物酶和硫氧还蛋白还原酶，在心血管氧化还原稳态中起着关键作用，代表心脏的一线酶抗氧化防御。人们越来越关注内质网 (ER) 中新兴的硒蛋白（一种多功能的细胞内细胞器，其功能障碍会引发心脏炎症和氧化应激，导致多种 CVD），它们在氧化还原平衡、抗氧化活性以及钙和 ER 稳态中起着至关重要的作用。 本综述重点介绍具有治疗潜力的内源性抗氧化策略，特别是硒蛋白，它们非常有前途，但值得更详细和临床研究。 选择性硒蛋白在胚胎发育中的重要性及其突变和先天性错误的后果突出表明需要提高对其在心肌氧化还原信号转导中的生物学功能的认识。这可能有助于为 CVD 的诊断、预防和治疗制定个性化方法。 40, 369-432.
