Proteomics Unit, Monzino Cardiology Center IRCCS, Milan, Italy.
Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Antioxid Redox Signal. 2021 Jan 1;34(1):49-98. doi: 10.1089/ars.2019.7955. Epub 2020 Aug 27.
Atherosclerotic cardiovascular diseases (ACVDs) continue to be a primary cause of mortality worldwide in adults aged 35-70 years, occurring more often in countries with lower economic development, and they constitute an ever-growing global burden that has a considerable socioeconomic impact on society. The ACVDs encompass diverse pathologies such as coronary artery disease and heart failure (HF), among others. It is known that oxidative stress plays a relevant role in ACVDs and some of its effects are mediated by lipid oxidation. In particular, lipid peroxidation (LPO) is a process under which oxidants such as reactive oxygen species attack unsaturated lipids, generating a wide array of oxidation products. These molecules can interact with circulating lipoproteins, to diffuse inside the cell and even to cross biological membranes, modifying target nucleophilic sites within biomolecules such as DNA, lipids, and proteins, and resulting in a plethora of biological effects. This review summarizes the evidence of the effect of LPO in the development and progression of atherosclerosis-based diseases, HF, and other cardiovascular diseases, highlighting the role of protein adduct formation. Moreover, potential therapeutic strategies targeted at lipoxidation in ACVDs are also discussed. The identification of valid biomarkers for the detection of lipoxidation products and adducts may provide insights into the improvement of the cardiovascular risk stratification of patients and the development of therapeutic strategies against the oxidative effects that can then be applied within a clinical setting.
动脉粥样硬化性心血管疾病（ACVDs）仍然是全球 35-70 岁成年人死亡的主要原因，在经济发展水平较低的国家更为常见，它们构成了一个不断增长的全球负担，对社会造成了相当大的社会经济影响。ACVDs 包括多种病理学，如冠状动脉疾病和心力衰竭（HF）等。已知氧化应激在 ACVDs 中起重要作用，其一些作用是通过脂质氧化介导的。特别是，脂质过氧化（LPO）是一种氧化剂（如活性氧物种）攻击不饱和脂质的过程，产生广泛的氧化产物。这些分子可以与循环脂蛋白相互作用，扩散到细胞内，甚至穿过生物膜，修饰生物分子（如 DNA、脂质和蛋白质）内的靶亲核位点，导致多种生物学效应。 本综述总结了 LPO 在动脉粥样硬化性疾病、HF 和其他心血管疾病的发展和进展中的作用的证据，强调了蛋白质加合物形成的作用。此外，还讨论了针对 ACVD 中脂质氧化的潜在治疗策略。 鉴定有效的生物标志物来检测脂质氧化产物和加合物，可能有助于改善患者的心血管风险分层，并制定针对氧化作用的治疗策略，然后可以在临床环境中应用。
