Simulated microgravity induces an inflammatory response in the common carotid artery of rats

Liu, Huan; Wang, Zhongchao; Yuan, Yue; Yu, Jin-Wen; Cai, Yuchen; Bai, Yuxiang; Zhang, Haijun; Bao, Jun-Xiang; Ren, Xue; Xie, Man‐Jiang; Ma, Jing

doi:10.1139/cjpp-2014-0066

Cited by 11 publications

(5 citation statements)

References 32 publications

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“…We limited our statistical analyses to five parameters, including traditional risk factors (SBP, total cholesterol, and LDL) (65), a biomarker of inflammation (hs-CRP), and a biomarker of oxidative stress (oxidized LDL). cIMT is thicker during active bouts of rheumatoid arthritis (79), and biomarkers of inflammation are elevated in the carotid artery of rats that experience carotid artery thickening during hindlimb suspension (50). Of the biomarkers we examined, only hs-CRP had a Fig.…”

Section: Discussionmentioning

confidence: 99%

Arterial structure and function during and after long-duration spaceflight

Lee

Ribeiro

Martin

et al. 2020

Journal of Applied Physiology

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Carotid artery structure and stiffness did not change on average in astronauts during long-duration spaceflight (<12 mo), despite increased oxidative stress and inflammation. Most oxidative stress and inflammation biomarkers returned to preflight levels soon after landing. Brachial artery structure and function also were unchanged by spaceflight. In this group of healthy middle-aged male and female astronauts, spaceflight in low Earth orbit does not appear to increase long-term cardiovascular health risk.

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Section: Discussionmentioning

confidence: 99%

Arterial structure and function during and after long-duration spaceflight

Lee

Ribeiro

Martin

et al. 2020

Journal of Applied Physiology

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“…The signals were detected using the Super Signal West substrate (Thermo Fisher Scientific, USA). Densitometry analyses of the western bands were performed using the Tanon Imaging software 67 .…”

Section: Methodsmentioning

confidence: 99%

miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity

Wang

Sun

et al. 2015

Sci Rep

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Recent studies have demonstrated that miRNAs can play important roles in osteoblast differentiation and bone formation. However, the function of miRNAs in bone loss induced by microgravity remains unclear. In this study, we investigated the differentially expressed miRNAs in both the femur tissues of hindlimb unloading rats and primary rat osteoblasts (prOB) exposed to simulated microgravity. Specifically, miR-132-3p was found up-regulated and negatively correlated with osteoblast differentiation. Overexpression of miR-132-3p significantly inhibited prOB differentiation, whereas inhibition of miR-132-3p function yielded an opposite effect. Furthermore, silencing of miR-132-3p expression effectively attenuated the negative effects of simulated microgravity on prOB differentiation. Further experiments confirmed that E1A binding protein p300 (Ep300), a type of histone acetyltransferase important for Runx2 activity and stability, was a direct target of miR-132-3p. Up-regulation of miR-132-3p by simulated microgravity could inhibit osteoblast differentiation in part by decreasing Ep300 protein expression, which, in turn, resulted in suppression of the activity and acetylation of Runx2, a key regulatory factor of osteoblast differentiation. Taken together, our findings are the first to demonstrate that miR-132-3p can inhibit osteoblast differentiation and participate in the regulation of bone loss induced by simulated microgravity, suggesting a potential target for counteracting decreases in bone formation.Numerous studies have shown that mechanical stimulations play an important role in the maintenance of bone homeostasis, skeletal morphology and strength during bone formation and development [1][2][3] . By contrast, skeletal unloading, as observed in space flight astronauts or in patients subjected to prolonged immobility or bed-rest, typically induces severe bone loss 4 . The early studies described similar phenomenon, such as cancellous osteoporosis in weight-bearing bones, decreased bone formation and abnormal bone metabolism after space flight 5,6 . During the spaceflight mission on the Soviet/Russian MIR spacecraft and the International Space Station, crew members experienced a persistently enhanced areal bone mineral density lost at an average monthly rate of 1.06% from the spine and 1.0 to 1.6% from the hip, despite adopting an intense exercise regimen to counteract mechanical unloading 7 . Decreased bone formation in both rat cortical and cancellous bones was also demonstrated by tetracycline labeling before and after space flight [8][9][10][11] . In view of spaceflight tremendous costs, more studies have been performed on the ground. The hindlimb unloading (HU) model is a well-tolerated method to mimic the cephalic fluid shift and removal of skeletal weight-bearing loads seen in spaceflight 12 . Despite the variability of data among independent studies, this model successfully replicates an osteopenia characterized by decreased bone mineral content, weakened bone resistance, and loss of femoral mass, simila...

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“…Ground-based simulated microgravity studies in HU rats and bed-resting humans have also revealed hypertrophy and increased vasoconstriction of the carotid artery (Hughson et al 2016;Zhang 2013). The mechanisms underlying the changes in artery function and structure may be related to the local renin-angiotensin system, endothelial nitric oxide synthase, ion channels, ras homolog family member A (Rho)/Rho kinase (ROCK), oxidative stress and inflammation (Liu et al 2014;Gao et al 2012;Ren et al 2011;Wu et al 2019;Zhang et al 2020b); however, clear evidence of arterial remodeling requires further exploration.…”

Section: Discussionmentioning

confidence: 99%

The OPG/RANKL/RANK system modulates calcification of common carotid artery in simulated microgravity rats by regulating NF-κB pathway

Liu

Cai

et al. 2022

Can. J. Physiol. Pharmacol.

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Functional and structural adaptation of common carotid artery could be one of the important causes of postflight orthostatic intolerance after microgravity exposure, the mechanisms of which remain unclear. Recent evidence indicates that long-term spaceflight increases carotid artery stiffness, which might present a high risk to astronaut health and postflight working ability. Studies have suggested that vascular calcification is a common pathological change in cardiovascular diseases that is mainly manifested as an increase in vascular stiffness. Therefore, this study investigated whether simulated microgravity induces calcification of common carotid artery and to elucidate the underlying mechanisms. Four-week-old hindlimb-unweighted (HU) rats were used to simulate the deconditioning effects of microgravity on cardiovascular system. We found that simulated microgravity induced vascular smooth muscle cell (VSMC) osteogenic differentiation and medial calcification, increased receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) and RANK expression, and enhanced NF-κB activation in rat common carotid artery. In vitro activation of the RANK pathway with exogenous RANKL, a RANK ligand, increased RANK and osteoprotegerin (OPG) expression in HU rats. Moreover, the expression of osteogenic markers and activation of NF-κB in HU rats were further enhanced by exogenous RANKL but suppressed by the RANK inhibitor osteoprotegerin fusion protein (OPG-Fc). These results indicated that the OPG/RANKL/RANK system modulates VSMC osteogenic differentiation and medial calcification of common carotid artery in simulated microgravity rats by regulating the NF-kB pathway.

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Simulated microgravity induces an inflammatory response in the common carotid artery of rats

Cited by 11 publications

References 32 publications

Arterial structure and function during and after long-duration spaceflight

Arterial structure and function during and after long-duration spaceflight

miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity

The OPG/RANKL/RANK system modulates calcification of common carotid artery in simulated microgravity rats by regulating NF-κB pathway

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