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Abstract
Adaptation of humans in low gravity conditions is a matter of utmost importance when efforts are on to a gigantic leap in human space expeditions for tourism and formation of space colonies. In this connection, cardiovascular adaptation in low gravity is a critical component of human space exploration. Deep high-throughput sequencing approach allowed us to analyze the miRNA and mRNA expression profiles in human umbilical cord vein endothelial cells (HUVEC), cultured under gravity (G), and stimulated microgravity (MG) achieved with a clinostat. The present study identified totally 1870 miRNAs differentially expressed in HUVEC under MG condition when compared to the cells subjected to unitary G conditions. The functional association of identified miRNAs targeting specific mRNAs revealed that miRNAs, hsa-mir-496, hsa-mir-151a, hsa-miR-296-3p, hsa-mir-148a, hsa-miR-365b-5p, hsa-miR-3687, hsa-mir-454, hsa-miR-155-5p, and hsa-miR-145-5p differentially regulated the genes involved in cell adhesion, angiogenesis, cell cycle, JAK-STAT signaling, MAPK signaling, nitric oxide signaling, VEGF signaling, and wound healing pathways. Further, the q-PCR based experimental studies of upregulated and downregulated miRNA and mRNAs demonstrate that the above reported miRNAs influence the cell proliferation and vascular functions of the HUVEC in MG conditions effectively. Consensus on the interactome results indicates restricted fluctuations in the transcriptome of the HUVEC exposed to short-term MG that could lead to higher levels of endothelial functions like angiogenesis and vascular patterning.
Highlights
Human physiology including the cardiovascular system has adapted to the constant orientation of the Earth’s gravity field and gravity vector throughout evolution[1]
Monolayers of human umbilical cord vein endothelial cells (HUVEC) were exposed to G and MG, respectively for 2 h followed by an overnight incubation, and after the overnight incubation, the cells were tested for viability, migration, and cell morphology
Fluorescein diacetate (FDA) staining indicates an increase in the number of live cells treated with 2 h MG (Fig. 1 a, b)
Summary
Human physiology including the cardiovascular system has adapted to the constant orientation of the Earth’s gravity field (static stimulation) and gravity vector (dynamic stimulation) throughout evolution[1]. In the era of rapid space exploration, it is obvious to experience the change in gravity by the human body. The cardiovascular system is one of the major systems affected due to the change in gravity among musculoskeletal, pulmonary, and immune systems[2]. Endothelium acts as mechano-transducers and responds to the mechanical and gravitational forces by undergoing various cytoskeletal changes that activate second messenger cascades, which, in turn, may act on specific response elements of affected genes[5]. The limited number of missions and high costs lower the possibility to perform experiments in real microgravity. To overcome these limitations, clinostats are used to simulate microgravity. We used our previously described 3D clinostat to simulate microgravity[12]
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