Pastushkova Lyudmila H, Rusanov Vasily B, Goncharova Anna G, Brzhozovskiy Alexander G, Kononikhin Alexey S, Chernikova Anna G, Kashirina Daria N, Nosovsky Andrey M, Baevsky Roman M, Nikolaev Evgeny N, Larina Irina M
Institute for Biomedical Problems - Russian Federation State Scientific Research Center Russian Academy of Sciences, Moscow, Russia.
V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
BMC Syst Biol. 2019 Mar 5;13(Suppl 1):17. doi: 10.1186/s12918-019-0688-9.
The strategy of adaptation of the human body in microgravity is largely associated with the plasticity of cardiovascular system regulatory mechanisms. During long-term space flights the changes in the stroke volume of the heart are observed, the heart rate decreases, the phase structure of cardiac cycle is readjusted The purpose of this work was to clarify urine proteome changes associated with the initial condition of the heart rate autonomic regulation mechanisms in cosmonauts who have participated in long space missions. Urine proteome of each cosmonaut was analyzed before and after space flight, depending on the initial parameters characterizing the regulatory mechanisms of the cardiovascular system.
The proteins cadherin-13, mucin-1, alpha-1 of collagen subunit type VI (COL6A1), hemisentin-1, semenogelin-2, SH3 domain-binding protein, transthyretin and serine proteases inhibitors realize a homeostatic role in individuals with different initial type of the cardiovascular system regulation. The role of significantly changed urine proteins in the cardiovascular homeostasis maintenance is associated with complex processes of atherogenesis, neoangiogenesis, activation of calcium channels, changes in cell adhesion and transmembrane properties, changes in extracellular matrix, participation in protection from oxidative stress and leveling the effects of hypoxia. Therefore, the concentrations of these proteins significantly differ between groups with dominant parasympathetic and sympathetic influences.
The space flight induced urine proteome changes are significantly different in the groups identified by heart rate autonomic regulation peculiarities before space flight. All these proteins regulate the associated biological processes which affect the stiffness of the vascular wall, blood pressure level, the severity of atherosclerotic changes, the rate and degree of age-related involution of elastin and fibulin, age-related increase in collagen stiffness, genetically determined features of elastin fibers. The increased vascular rigidity (including the aorta) and of myocardium may be regarded as a universal response to various extreme factors. Significant differences in the semi-quantitative analysis of signal proteins between groups with different types of autonomic regulation are explained by a common goal: to ensure optimal adaptation regardless of age and of the genetically determined type of responses to the extreme environmental factors effects.
人体在微重力环境下的适应策略很大程度上与心血管系统调节机制的可塑性相关。在长期太空飞行期间，会观察到心脏每搏输出量的变化、心率下降以及心动周期的相位结构重新调整。这项研究的目的是阐明参与长期太空任务的宇航员尿液蛋白质组变化与心率自主调节机制初始状态之间的关系。根据表征心血管系统调节机制的初始参数，分析每位宇航员在太空飞行前后的尿液蛋白质组。
钙黏蛋白-13、黏蛋白-1、VI型胶原亚基α-1（COL6A1）、半腱蛋白-1、精液凝胶蛋白-2、SH3结构域结合蛋白、转甲状腺素蛋白和丝氨酸蛋白酶抑制剂在具有不同心血管系统调节初始类型的个体中发挥稳态作用。尿液中显著变化的蛋白质在维持心血管稳态中的作用与动脉粥样硬化形成、新生血管生成、钙通道激活、细胞黏附和跨膜特性改变、细胞外基质变化、参与抗氧化应激保护以及减轻缺氧影响等复杂过程相关。因此，这些蛋白质的浓度在以副交感神经和交感神经影响为主的组之间存在显著差异。
太空飞行引起的尿液蛋白质组变化在根据太空飞行前心率自主调节特点划分的组中存在显著差异。所有这些蛋白质调节相关的生物学过程，这些过程会影响血管壁的硬度、血压水平、动脉粥样硬化变化的严重程度、弹性蛋白和纤维蛋白与年龄相关的退化速率和程度、与年龄相关的胶原硬度增加以及弹性纤维的遗传决定特征。血管（包括主动脉）和心肌刚度的增加可被视为对各种极端因素的普遍反应。不同自主调节类型组之间信号蛋白半定量分析的显著差异是由一个共同目标解释的：无论年龄和对极端环境因素影响的遗传决定反应类型如何，都要确保最佳适应。
