ABSTRACT
Individuals exposed to extended periods of spaceflight or prolonged 6° head-down-tilt bed rest often suffer from health hazards represented by cardiovascular deconditioning. Many studies have reported that alterations in vascular endothelial cells contribute to cardiovascular dysfunction induced by microgravity. Autophagy, a lysosomal degradation pathway, serves an adaptive role for survival, differentiation, and development in cellular homeostasis, and can be triggered by various environmental stimuli. However, whether autophagy can be induced in endothelial cells by real or simulated microgravity remains to be determined. This study was designed to investigate the effects of simulated microgravity on the activation of autophagy in human umbilical vein endothelial cells (HUVECs). We report here that clinorotation, a simulated model of microgravity, enhances autophagosome formation, increases LC3 and beclin-1 expression, and promotes the conversion of LC3-I to LC3-II in HUVECs. These results demonstrate that simulated microgravity for 48 h activates autophagy of vascular endothelial cells.
Subject(s)
Autophagy , Human Umbilical Vein Endothelial Cells/metabolism , Rotation/adverse effects , Weightlessness/adverse effects , Apoptosis Regulatory Proteins/biosynthesis , Beclin-1 , Cardiovascular Deconditioning/physiology , Cell Line , Humans , Membrane Proteins/biosynthesis , Microtubule-Associated Proteins/biosynthesis , Microtubule-Associated Proteins/metabolism , Space FlightABSTRACT
We have shown previously that combined short-arm centrifuge and aerobic exercise training preserved several physiologically important cardiovascular functions in humans. We hypothesized that artificial gravity (AG) and exercise is effective to prevent changes of physical problems during head-down bed rest (HDBR). To test this hypothesis, 12 healthy male subjects had undergone 4 days of 6° HDBR. Six of them were exposed to AG of an alternating 2-min intervals of +1.0 and +2.0 Gz at foot level for 30 min twice per day with ergometric exercise of 40 W as a countermeasure during bed rest (CM group), while the remaining six served as untreated controls (no-CM group). Before and after 4 days of bed rest, leg venous hemodynamics was assessed by venous occlusion plethysmography and autonomic cardiovascular control estimated by power spectral analysis of blood pressure and heart rate. Further, orthostatic tolerance was evaluated by a 75° head-up tilt test and physical working capacity was surveyed by near maximal physical working capacity test before and after bed rest. The data showed that combined centrifuge and exercise applied twice daily for a total of 60 min during 4 days of HDBR prevented (a) a decrease in working capacity, (b) autonomic dysfunction (a decrease in the activity of parasympathetic cardiac innervation) and (c) an increase in leg venous flow resistance. The combination of a 30 min alternating of +1.0 and +2.0 Gz for twice per day of AG with 40 W ergometric exercise may offer a promising countermeasure to short duration simulated microgravity.