Simulated Microgravity Exposure Modulates the Phenotype of Cultured Vascular Smooth Muscle Cells
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ORIGINAL PAPER
Simulated Microgravity Exposure Modulates the Phenotype of Cultured Vascular Smooth Muscle Cells Hongyan Kang • Yubo Fan • Anqiang Sun Xiaoling Jia • Xiaoyan Deng
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Published online: 25 October 2012 Ó Springer Science+Business Media New York 2012
Abstract Evidence from ground-based animal studies using tail-suspended hindlimb unloaded rats model has clearly demonstrated that simulated microgravity-induced smooth muscle cell phenotype conversion, a characteristic vascular structural and functional remodeling, may be one of the key contributors to postspaceflight orthostatic intolerance. However, the rats model involves multiple collective effects of microgravity including cephalic fluid shift and postural muscle unloading on smooth muscle cells (SMCs). It cannot isolate a single factor from the collective ones and therefore is not ideal to study the effects of gravitational vector alteration alone on SMCs. To test the hypothesis that gravitational vector alteration per se might affect smooth muscle cell phenotype, a roller culture apparatus was employed to expose cultured rat aortic smooth muscle cells (RASMCs) to simulated microgravity. Cell proliferation, cell cycle distribution, apoptosis, migration, and nitric oxide production rates were measured and compared between the control and the simulated microgravity groups. Cell cytoskeleton reorganization induced by simulated microgravity was observed by confocal microscopy. Specific contractile and synthetic Gene expression at the mRNA level was quantified by reverse transcriptional polymerase chain reaction. It was observed that simulated microgravity suppressed RASMC proliferation and migration, enhanced cell apoptosis, stimulated NO release, and destroyed the original well-organized cytoskeleton. Moreover, at the mRNA level, long-time
H. Kang Y. Fan A. Sun X. Jia X. Deng (&) Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China e-mail: [email protected]
exposure (C72 h) to simulated microgravity induced a contractile phenotype tendency by up-regulating smMHC expression. All these findings suggest that the phenotype modulation of vascular smooth muscle cells may be gravity dependent. Keywords Simulated microgravity RASMC Phenotype modulation
Introduction Astronauts exposed to microgravity often experience orthostatic intolerance and reduced excise capacity on return to Earth [1]. Symptoms experienced during standing include increased heart rate, orthostatic hypotension, and frank syncope [2]. This impaired orthostatic stability may be among the highest risks to the safety, well-being, and performances of astronauts [3]. Although after several decades of study, mechanisms responsible for orthostatic intolerance are disputed and multiple, including hypovolemia, cardiovascular structural changes, and alterations in central integration, baroreceptor function, and neurohumoral regulation [4], among which, microgravit
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