PMID- 28357491 OWN - NLM STAT- MEDLINE DCOM- 20180305 LR - 20181113 IS - 1432-2013 (Electronic) IS - 0031-6768 (Linking) VI - 469 IP - 5-6 DP - 2017 Jun TI - Acid sphingomyelinase/ceramide regulates carotid intima-media thickness in simulated weightless rats. PG - 751-765 LID - 10.1007/s00424-017-1969-z [doi] AB - 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. FAU - Cheng, Yao-Ping AU - Cheng YP AD - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. FAU - Zhang, Hai-Jun AU - Zhang HJ AD - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. FAU - Su, Yu-Ting AU - Su YT AD - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. FAU - Meng, Xing-Xing AU - Meng XX AD - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. FAU - Xie, Xiao-Ping AU - Xie XP AD - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. FAU - Chang, Yao-Ming AU - Chang YM AD - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. FAU - Bao, Jun-Xiang AU - Bao JX AD - Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. baojunx@fmmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170329 PL - Germany TA - Pflugers Arch JT - Pflugers Archiv : European journal of physiology JID - 0154720 RN - 0 (Ceramides) RN - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase) SB - IM MH - Animals MH - Apoptosis MH - Carotid Arteries/cytology/*metabolism MH - Cell Proliferation MH - Ceramides/*metabolism MH - Hindlimb Suspension/*adverse effects MH - Male MH - Myocytes, Smooth Muscle/*metabolism/physiology MH - Rats MH - Rats, Sprague-Dawley MH - Sphingomyelin Phosphodiesterase/genetics/*metabolism MH - Tunica Intima/cytology/*metabolism OTO - NOTNLM OT - Acid sphingomyelinase OT - Ceramide OT - Common carotid artery OT - Intima-media thickness OT - Simulated weightlessness OT - Vascular remodeling EDAT- 2017/03/31 06:00 MHDA- 2018/03/06 06:00 CRDT- 2017/03/31 06:00 PHST- 2016/10/18 00:00 [received] PHST- 2017/03/20 00:00 [accepted] PHST- 2017/03/08 00:00 [revised] PHST- 2017/03/31 06:00 [pubmed] PHST- 2018/03/06 06:00 [medline] PHST- 2017/03/31 06:00 [entrez] AID - 10.1007/s00424-017-1969-z [pii] AID - 10.1007/s00424-017-1969-z [doi] PST - ppublish SO - Pflugers Arch. 2017 Jun;469(5-6):751-765. doi: 10.1007/s00424-017-1969-z. Epub 2017 Mar 29.