Simulated microgravity promotes monocyte adhesion to rat aortic endothelium via nuclear factor-κB activation.
Microgravity-induced vascular remodelling may play an important role in post-spaceflight orthostatic intolerance. In this study, we aimed to investigate the effects of simulated microgravity on monocyte adhesion to aortic endothelium in hindlimb unweighted rats and to elucidate the underlying mechanisms associated with this event. Sprague-Dawley rats were subjected to 4-week hindlimb unweighting to simulate microgravity. The recruitment of monocytes to the abdominal aorta was investigated by en face immunofluorescence staining and monocyte binding assays. The expression of the adhesion molecules E-selectin and vascular cell adhesion molecule-1 as well as the cytokine monocyte chemoattractant protein (MCP)-1 was evaluated by immunohistochemical staining, western blot, and quantitative reverse transcription polymerase chain reaction analyses. Additionally, nuclear factor-κB (NF-κB) activation and the messenger RNA expression levels of E-selectin, vascular cell adhesion molecule-1, and MCP-1 were assessed with the administration of an NF-κB inhibitor, pyrrolidine dithiocarbamate. Results showed that simulated microgravity significantly increased monocyte recruitment to the aortic endothelium, protein expression of E-selectin and MCP-1, and NF-κB activation in the abdominal aorta of rats. Pyrrolidine dithiocarbamate treatment not only significantly inhibited NF-κB activity but also reduced the messenger RNA levels of E-selectin, vascular cell adhesion molecule-1, and MCP-1 as well as monocyte recruitment in the abdominal aorta of hindlimb unweighted rats. These results suggest that simulated microgravity increases monocyte adhesion to rat aortic endothelium via the NF-κB-mediated expression of the adhesion molecule E-selectin and the cytokine MCP-1. Therefore, an NF-κB-mediated inflammatory response may be one of the cellular mechanisms responsible for arterial remodelling during exposure to microgravity.
Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China.
Huan
H
Liu
Zhong-Chao
ZC
Wang
Yun-Gang
YG
Bai
Yue
Y
Cai
Jin-Wen
JW
Yu
Hai-Jun
HJ
Zhang
Jun-Xiang
JX
Bao
Xin-Ling
XL
Ren
Man-Jiang
MJ
Xie
Jin
J
Ma
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology*; D002448:Cell Adhesion / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D018474:Weightlessness Simulation
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D019040:E-Selectin; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D019010:Vascular Cell Adhesion Molecule-1; C020972:pyrrolidine dithiocarbamic acid
NF-κB; arterial remodelling; inflammatory response; simulated microgravity