Microgravity-induced stress mechanisms in human stem cell-derived cardiomyocytes

Area of Science:

• Cardiovascular Science
• Space Medicine
• Cell Biology

Background:

• Exposure to microgravity in spaceflight is a risk factor for cardiovascular diseases.
• Cardiomyocytes (CMs) are crucial for heart function and can be affected by altered gravity.
• Understanding microgravity's cellular effects is vital for astronaut health and developing countermeasures.

Purpose of the Study:

• To investigate the impact of simulated microgravity (SMG) on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
• To elucidate the molecular mechanisms underlying microgravity-induced cardiac dysfunction.
• To identify potential therapeutic targets for spaceflight-related cardiovascular pathologies.

Main Methods:

• Derivation of hiPSC-CMs from human-induced pluripotent stem cells.
• Application of simulated microgravity (SMG) conditions.
• Integration of multi-omics approaches (genomics, transcriptomics, proteomics) and chromosome conformation capture (3C).
• Live-cell imaging of transgenic cardiomyocyte models.

Main Results:

• SMG significantly impairs cardiomyocyte contractile velocity and overall function.
• Microgravity exposure induces cellular senescence in cardiomyocytes.
• SMG alters mitochondrial function, increasing reactive oxygen species (ROS) generation and affecting energy metabolism.
• A novel microgravity-controlled axis responsible for cardiomyocyte contractile dysfunction was identified.

Conclusions:

• Simulated microgravity triggers senescence pathways in human cardiomyocytes, leading to functional decline.
• Mitochondrial dysfunction and oxidative stress are key mediators of microgravity-induced cardiac impairment.
• These findings provide insights into spaceflight-associated cardiovascular risks and suggest strategies for prevention and treatment of senescence-related diseases.