Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland.
Student's Scientific Association, Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland.
Int J Mol Sci. 2024 Nov 20;25(22):12467. doi: 10.3390/ijms252212467.
The literature analysis conducted in this review discusses the latest achievements in the identification of cardiovascular damage induced by oxidative stress with secondary platelet mitochondrial dysfunction. Damage to the platelets of mitochondria as a result of their interactions with reactive oxygen species (ROS) and reactive nitrogen species (RNS) can lead to their numerous ischemic events associated with hypoxia or hyperoxia processes in the cell. Disturbances in redox reactions in the platelet mitochondrial membrane lead to the direct oxidation of cellular macromolecules, including nucleic acids (DNA base oxidation), membrane lipids (lipid peroxidation process) and cellular proteins (formation of reducing groups in repair proteins and amino acid peroxides). Oxidative changes in biomolecules inducing tissue damage leads to inflammation, initiating pathogenic processes associated with faster cell aging or their apoptosis. The consequence of damage to platelet mitochondria and their excessive activation is the induction of cardiovascular and neurodegenerative diseases (Parkinson's and Alzheimer's), as well as carbohydrate metabolism disorders (diabetes). The oxidation of mitochondrial DNA can lead to modifications in its bases, inducing the formation of exocyclic adducts of the ethano and propano type. As a consequence, it disrupts DNA repair processes and conduces to premature neoplastic transformation in critical genes such as the suppressor gene, which leads to the development of various types of tumors. The topic of new innovative methods and techniques for the analysis of oxidative stress in platelet mitochondria based on methods such as a nicking assay, oxygen consumption assay, Total Thrombus formation Analysis System (T-Tas), and continuous-flow left ventricular assist devices (CF-LVADs) was also discussed. They were put together into one scientific and research platform. This will enable the facilitation of faster diagnostics and the identification of platelet mitochondrial damage by clinicians and scientists in order to implement adequate therapeutic procedures and minimize the risk of the induction of cardiovascular diseases, including ischemic events correlated with them. A quantitative analysis of the processes of thrombus formation in cardiovascular diseases will provide an opportunity to select specific anticoagulant and thrombolytic drugs under conditions of preserved hemostasis.
这篇文献综述分析讨论了最新的研究成果，即通过鉴定氧化应激引起的心血管损伤与血小板线粒体功能障碍之间的关系。血小板与活性氧（ROS）和活性氮（RNS）相互作用，导致线粒体受损，进而引发与细胞缺氧或富氧过程相关的多种缺血性事件。血小板线粒体膜中氧化还原反应的紊乱会导致细胞大分子的直接氧化，包括核酸（DNA 碱基氧化）、膜脂质（脂质过氧化过程）和细胞蛋白（修复蛋白和氨基酸过氧化物中还原基团的形成）。生物分子的氧化变化会导致组织损伤，引发炎症，启动与细胞更快衰老或细胞凋亡相关的致病过程。血小板线粒体损伤及其过度激活的后果是诱导心血管和神经退行性疾病（帕金森病和阿尔茨海默病）以及碳水化合物代谢紊乱（糖尿病）。线粒体 DNA 的氧化会导致其碱基发生修饰，诱导形成乙撑和丙撑型的环外加合物。因此，它会破坏 DNA 修复过程，并导致关键基因（如抑癌基因）的过早癌变转化，从而导致各种类型的肿瘤的发展。本研究还讨论了基于缺口分析、耗氧量测定、全血栓形成分析系统（T-Tas）和连续流动左心室辅助装置（CF-LVADs）等方法分析血小板线粒体氧化应激的新的创新方法和技术，并将它们整合到一个科学研究平台中。这将有助于临床医生和科学家更快地进行诊断，并识别血小板线粒体损伤，以便实施适当的治疗程序，最大程度地降低诱导心血管疾病的风险，包括与这些疾病相关的缺血性事件。对心血管疾病中血栓形成过程的定量分析将为在保持止血的情况下选择特定的抗凝和溶栓药物提供机会。
