Prolonged Exposure to Microgravity Reduces Cardiac Contractility and Initiates Remodeling in Drosophila

Abstract

Highlights d Flies in microgravity exhibit cardiac constriction, remodeling, and diminished output d Heart defects correlate with reduced sarcomeric and extracellular matrix gene expression d Proteosome gene or protein expression is upregulated, suggesting proteostasis imbalance

Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart

“…Whereas cardiovascular physiology has been studied intensively in astronauts, analysis of cardiac changes at the tissue level has been more limited [12,13,[34][35][36]. Goldstein et al [12] report that spaceflight (14 days) reduces the cross-sectional area of papillary cardiomyocytes in rats relative to ground controls, with ultrastructural changes consistent with cardiac atrophy.…”

“…More recently, long duration spaceflight (37 days) was shown to alter expression of methylationrelated genes in the heart of adult mice, but not cytoskeletal protein levels. Interestingly, lifetime exposure of Drosophila to microgravity leads to diminished cardiac size, cardiac dysfunction, altered remodeling, and proteosomal abnormalities [36]. Furthermore, spaceflight causes cardiac progenitor cells in culture to display a gene expression profile consistent with early, stem-like function along with increased oxidative stress and re-entry into the cell cycle [37].…”

WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity

“…They reported the effects of microgravity on heart function in WT fruit flies that were born, developed, and spent 1-3 weeks as adults aboard the ISS compared with their ground-based controls, the results showed that structural and functional cardiac remodeling occurs in response to microgravity; RNA sequencing and immunohistochemistry data suggested that alterations in proteostasis likely contribute to the observed changes in cardiac remodeling induced by microgravity (Walls et al, 2020). According to their research, cardiac atrophy mediated by protein homeostasis regulation may be a fundamental response of the heart muscle to microgravity (Walls et al, 2020). Protein ubiquitination is a multi-functional post-translational modification that affects a variety of disease processes, including cardiac remodeling (Willis et al, 2010).…”

“…Our organ systems have evolved to work under 1 g environment. It is not yet clear what effects will be produced by long-term exposure to low-gravity environments and how these effects will be manifested at the cellular and molecular levels ( Walls et al, 2020 ). Since the first human went into space, cardiac health has been a major concern of the world’s space agencies; however, the clinical evidence for decreased function and unmasking of asymptomatic cardiovascular disease is limited.…”

“…Our previous studies have shown that pathological cardiac remodeling signals (such as HDAC4) were activated in the heart of mice after tail suspension, which may lead to cardiac remodeling and decline in function ( Zhong et al, 2016 ; Ling et al, 2018 ). Walls et al (2020) found that exposure to microgravity aboard the International Space Station (ISS) caused heart dysfunction in a fly cardiac model: hearts are less contractile and exhibit changes in genes and proteins that maintain heart structure and function; among which, it is worth noting that proteasome gene expression was upregulated, suggesting that the regulation of protein homeostasis mediated by ubiquitination modification plays an important role in myocardial remodeling caused by microgravity.…”