title: Acid sphingomyelinase/ceramide regulates carotid intima-media thickness in simulated weightless rats.
abstract: Structural adaptation of arteries to weightlessness might lower the working ability or even threaten the physical health of astronauts, but the underlying mechanism is unclear. Acid sphingomyelinase (ASM) catalyzes ceramide (Cer) generation controlling arterial remodeling through multiple signaling pathways. In the present study, we aimed to investigate the contribution of ASM/Cer to the changes of common carotid artery intima-media thickness (CIMT) induced by simulated weightlessness. Hindlimb-unloaded tail-suspended (HU) rats were used to simulate the effect of weightlessness. Morphology of the carotid artery (CA) was examined by hematoxylin-eosin staining. Protein content of ASM or proliferating cell nuclear antigen (PCNA) was detected by Western blot. Cer level was measured by immunohistochemistry analysis. Apoptosis events were observed by transferase-mediated dUTP nick end labeling (TUNEL) staining. During 4 weeks of tail suspension, CIMT was increased gradually in HU but not in their synchronous control rats (P < 0.05). Correspondingly, the CA of HU rats had a lower apoptosis and higher proliferation of vascular smooth muscle cells (VSMCs). As compared to the control, both ASM protein expression and Cer content were reduced significantly in CA of HU rats (P < 0.05), incubation of which with permeable Cer reversed the changes in apoptosis and proliferation substantially. Furthermore, when the ASM protein content as well as Cer level in CA of control rats was diminished by using an ASM inhibitor, an increase of CIMT along with reduced apoptosis and enhanced proliferation of VSMCs was found. Our results suggest that by controlling the balance between apoptosis and proliferation, ASM/Cer plays an important role in the regulation of CIMT during simulated weightlessness.
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yao-Ping
authors.initials: YP
authors.lastname: Cheng
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Su
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Meng
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Xie
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yao-Ming
authors.initials: YM
authors.lastname: Chang
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. baojunx@fmmu.edu.cn.
authors.forename: Jun-Xiang
authors.initials: JX
authors.lastname: Bao
mesh_terms: D000818:Animals; D017209:Apoptosis; D002339:Carotid Arteries / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D002518:Ceramides / Q000378:metabolism*; D019417:Hindlimb Suspension / Q000009:adverse effects*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D017539:Tunica Intima / Q000166:cytology / Q000378:metabolism*
chemical_list: D002518:Ceramides; D013108:Sphingomyelin Phosphodiesterase
keywords: Acid sphingomyelinase; Ceramide; Common carotid artery; Intima-media thickness; Simulated weightlessness; Vascular remodeling