title: Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart.
abstract: Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age. Simulated microgravity exposure did not impact AKT or ERK phosphorylation levels and did not influence cell migration, but elevated transcripts for paracrine factors were identified in neonatal and adult cardiovascular progenitors. Age-dependent responses surfaced when comparing the impact of microgravity on differentiation. Endothelial cell tube formation was unchanged or increased in progenitors from adults whereas neonatal cardiovascular progenitors showed a decline in tube formation (p<0.05). Von Willebrand Factor, an endothelial differentiation marker, and MLC2v and Troponin T, markers for cardiomyogenic differentiation, were elevated in expression in adult progenitors after simulated microgravity. DNA repair genes and telomerase reverse transcriptase which are highly expressed in early stem cells were increased in expression in neonatal but not adult cardiac progenitors after growth under simulated microgravity conditions. Neonatal cardiac progenitors demonstrated higher levels of MESP1, OCT4, and brachyury, markers for early stem cells. MicroRNA profiling was used to further investigate the impact of simulated microgravity on cardiovascular progenitors. Fifteen microRNAs were significantly altered in expression, including microRNAs-99a and 100 (which play a critical role in cell dedifferentiation). These microRNAs were unchanged in adult cardiac progenitors. The effect of exposure to simulated microgravity in cardiovascular progenitors is age-dependent. Adult cardiac progenitors showed elevated expression of markers for endothelial and cardiomyogenic differentiation whereas neonatal progenitors acquired characteristics of dedifferentiating cells.
authors.affiliation: Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Tania I
authors.initials: TI
authors.lastname: Fuentes
authors.affiliation: Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Appleby
authors.affiliation: Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Raya
authors.affiliation: Department of and Cardiothoracic Surgery, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Leonard
authors.initials: L
authors.lastname: Bailey
authors.affiliation: Department of and Cardiothoracic Surgery, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Nahidh
authors.initials: N
authors.lastname: Hasaniya
authors.affiliation: BioServe Space Technologies, Department of Aerospace Engineering Sciences, University of Colorado, Boulder, Colorado, United States of America.
authors.forename: Louis
authors.initials: L
authors.lastname: Stodieck
authors.affiliation: Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Kearns-Jonker
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002469:Cell Separation / Q000379:methods*; D004260:DNA Repair / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D018474:Weightlessness Simulation
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases