Wang Hongjiang, Li Xiangru, Wang Moye, Ma Anqi, Research Department of Characteristic Medical Center (formerly 306 Hospital).
Edited by Liu Yan/Cui Yan, Medical Science Popularization Center
The space environment (microgravity, radiation, circadian rhythm changes, etc.) poses a serious threat to the health of astronauts, and astronauts will face many risks during long-term space flight, including multi-organ degeneration, dysfunction, structural abnormalities, metabolic disorders, and premature aging. For the astronaut cardiovascular system, space flight can lead to symptoms such as decreased heart rate, decreased arterial pressure, arrhythmias, cardiac atrophy, anemia, and other aging disorders. At present, the mechanism of cardiac abnormalities in microgravity environment is not fully understood, and there is still a lack of effective treatment and prevention methods for cardiovascular system symptoms caused by the space environment, and further exploration of countermeasures is needed.
Thiamine, also known as vitamin B1, is an important water-soluble vitamin that cannot be synthesized in living organisms and is mainly involved in the metabolism of carbohydrates and amino acids in the body. Thiamine deficiency reduces the efficiency of the tricarboxylic acid (TCA) cycle and impairs ATP production. Thiamine supplementation reduces the risk and improves cardiovascular outcomes.
In this study, cardiomyocytes that induce pluripotent stem cell differentiation were sent to the space station by the Shenzhou-13 spacecraft, and the calcium-fluorescent probe scintillation signal synchronized with the autonomous pulsation of cardiomyocytes was recorded in space. Furthermore, the research team has made breakthroughs in analyzing the mechanism of space microgravity effects in human cardiomyocytes through a combination of space experiments and ground-based microgravity simulation experiments, and the main conclusions are as follows.
Under spatial microgravity, cardiomyocytes undergo adaptive changes.
The spatial environment can lead to sarcomere rearrangement of cardiomyocytes and abnormal expression of genes related to calcium cycle, resulting in altered cardiomyocyte contractility. The research team further found that space microgravity exposed the alteration of thiamine utilization in cardiomyocytes, and thiamine, a coenzyme of a key catalytic enzyme in the TCA cycle, significantly inhibited cellular uptake in microgravity.
Thiamine supplementation antagonizes the effects of microgravity on cardiomyocytes.
The research team found that thiamine supplementation was effective in counteracting the attenuation of microgravity-induced cardiomyocyte beating rate and Ca2+ processing capacity. In addition, thiamine supplementation can protect cardiomyocytes from microgravity-induced cytoskeletal remodeling and depolymerization. Mechanistically, the research team found that the abnormal expression of thiamine channel proteins SLC19A2 an important cause of abnormal thiamine intake, and that by regulating the expression of SLC19A2, it can improve the metabolic abnormalities, lactate increase, and oxidative phosphorylation defects caused by simulated microgravity, which is expected to be a new therapeutic target.
Thiamine treatment alleviates cardiac insufficiency in mice caused by simulated weight loss.
The research team used an animal model of mice suspended at 30° head for 28 days to evaluate the effect of thiamine supplementation, and found that thiamine supplementation could significantly reverse the myocardial atrophy phenotype of the model mice, improve cardiac systolic and diastolic function, and significantly increase the amount of ATP produced and reduce the lactate content of TS mice. This section suggests that thiamine supplementation can protect the mouse heart from structural and functional alterations caused by simulated microgravity.
In summary, the research team found that cardiomyocytes adapt to the microgravity environment by reducing TCA cycle efficiency and ATP production during space flight, and maintain low-energy metabolic homeostasis. Supplementation with thiamine can significantly reduce the phenotype of cardiomyocyte and cardiac structural and functional adaptation in a simulated microgravity environment. Thiamine may be a potential means to resist the structural and functional adaptation of cardiomyocytes induced by microgravity environment, and has potential translational application value.
The research paper was published in April 2024 in Signal Transduction and Targeted Therapy (CAS Zone 1, IF=39.3). Professor Hu Shijun and Professor Shen Zhenya from the First Affiliated Hospital of Soochow University School of Medicine and the State Key Laboratory of Radiation Medicine and Protection of Soochow University, Professor Li Yinghui from the China Astronaut Research and Training Center and the State Key Laboratory of Aerospace Medicine are the co-corresponding authors of the paper, and Han Xinglong from the First Affiliated Hospital of Soochow University School of Medicine and researcher Qu Lina from the China Astronaut Research and Training Center are the co-first authors of the article. This work is also strongly supported by Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology.
(Some of the pictures come from the Internet)