Cardiac function, structural, and electrical remodeling by microgravity exposure

Sy, Mary R.; Keefe, Joshua; Sutton, Jeffrey P.; Wehrens, Xander H.T.

doi:10.1152/ajpheart.00611.2022

Cited by 11 publications

(5 citation statements)

References 118 publications

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“…From the cardiovascular perspective, cardiac output and stroke volume initially increase upon exposure to microgravity, but subsequently decline, along with cardiac muscle mass ( 7 , 8 ). Peripheral vasodilation predominates and is exacerbated by changes in autonomic receptor sensitivities, endothelial changes, and vascular remodeling ( 9 , 10 ).…”

Section: Physiologic Consequences Of Spaceflightmentioning

confidence: 99%

Space exploration as a catalyst for medical innovations

2023

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Aerospace research has a long history of developing technologies with industry-changing applications and recent history is no exception. The expansion of commercial spaceflight and the upcoming exploration-class missions to the Moon and Mars are expected to accelerate this process even more. The resulting portable, wearable, contactless, and regenerable medical technologies are not only the future of healthcare in deep space but also the future of healthcare here on Earth. These multi-dimensional and integrative technologies are non-invasive, easily-deployable, low-footprint devices that have the ability to facilitate rapid detection, diagnosis, monitoring, and treatment of a variety of conditions, and to provide decision-making and performance support. Therefore, they are primed for applications in low-resource and remote environments, facilitating the extension of quality care delivery to all patients in all communities and empowering non-specialists to intervene early and safely in order to optimize patient-centered outcomes. Additionally, these technologies have the potential to advance care delivery in tertiary care centers by improving transitions of care, providing holistic patient data, and supporting clinician wellness and performance. The requirements of space exploration have created a number of paradigm-altering medical technologies that are primed to revitalize and elevate our standard of care here on Earth.

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Section: Physiologic Consequences Of Spaceflightmentioning

confidence: 99%

Space exploration as a catalyst for medical innovations

2023

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“…Because of the critical role of the heart in maintaining proper bodily systemic functions, a series of studies have been carried out in rodent and cell models to investigate the effects of microgravity on cardiac physiology, metabolism, and cellular biology. [7][8][9][10] In Drosophila, microgravity reduces heart size, contractility, and proteostasis imbalance. 11 The potential mechanisms underpinning adverse cardiac dysfunction or adaptation in response to microgravity include decreased metabolism, alerted calcium handling, increased oxidative stress, inflammation, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity

Han,

Qu,

et al. 2024

Sig Transduct Target Ther

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During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

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“…This often results from inactivity and unloading triggered by such events as prolonged bed rest or space flight. Exercise during these circumstances can mitigate some of the problems [1–3]. An enlarged, dilated cardiomyopathic heart in failure is also weak, and some mitigation with reverse remodeling can result by the use of a left ventricular assist device (LVAD) as a bridge to transplant [4–6].…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte external mechanical unloading activates modifications of α‐actinin differently from sarcomere‐originated unloading

et al. 2023

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Loss of myocardial mass in a neonatal rat cardiomyocyte culture is studied to determine whether there is a distinguishable cellular response based on the origin of mechano‐signals. The approach herein compares the sarcomeric assembly and disassembly processes in heart cells by imposing mechano‐signals at the interface with the extracellular matrix (extrinsic) and at the level of the myofilaments (intrinsic). Experiments compared the effects of imposed internal (inside/out) and external (outside/in) loading and unloading on modifications in neonatal rat cardiomyocytes. Unloading of the cellular substrate by myosin inhibition (1μM mavacamten), or cessation of cyclic strain (1 Hz, 10% strain) after preconditioning, led to significant disassembly of sarcomeric α‐actinin by 6 hrs. In myosin inhibition, this was accompanied by redistribution of intracellular poly‐ubiquitin K48 to the cellular periphery relative to the poly‐ubiquitin K48 reservoir at the I‐band. Moreover, loading and unloading of the cellular substrate led to a three‐fold increase in post translational modifications (PTMs) when compared to the myosin‐specific activation or inhibition. Specifically, phosphorylation increased with loading while ubiquitination increased with unloading, which may involve ERK1/2 and FAK activation. The identified PTMs, including ubiquitination, acetylation, and phosphorylation, are proposed to modify internal domains in α‐actinin to increase its propensity to bind F‐actin. These results demonstrate a link between mechanical feedback and sarcomere protein homeostasis via PTMs of α‐actinin that exemplify how cardiomyocytes exhibit differential responses to the origin of force. The implications of sarcomere regulation governed by PTMs of α‐actinin are discussed with respect to cardiac atrophy and heart failure.

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Cardiac function, structural, and electrical remodeling by microgravity exposure

Cited by 11 publications

References 118 publications

Space exploration as a catalyst for medical innovations

Space exploration as a catalyst for medical innovations

Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity

Cardiomyocyte external mechanical unloading activates modifications of α‐actinin differently from sarcomere‐originated unloading

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