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BMAL1 Disrupted Intrinsic Diurnal Oscillation in Rat Cerebrovascular Contractility of Simulated Microgravity Rats by Altering Circadian Regulation of miR-103/CaV1.2 Signal Pathway

1
Department of Aerospace Physiology, Key Laboratory of Aerospace Medicine of Ministry of Education, Fourth Military Medical University, Xi’an 710032, China
2
Department of Physiology, Fourth Military Medical University, Xi’an 710032, China
3
First Cadet Brigade, Fourth Military Medical University, Xi’an 710032, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 3947; https://doi.org/10.3390/ijms20163947
Received: 12 June 2019 / Revised: 17 July 2019 / Accepted: 6 August 2019 / Published: 14 August 2019
(This article belongs to the Special Issue Channels and Transporters in Cells and Tissues)
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Abstract

The functional and structural adaptations in cerebral arteries could be one of the fundamental causes in the occurrence of orthostatic intolerance after space flight. In addition, emerging studies have found that many cardiovascular functions exhibit circadian rhythm. Several lines of evidence suggest that space flight might increase an astronaut’s cardiovascular risks by disrupting circadian rhythm. However, it remains unknown whether microgravity disrupts the diurnal variation in vascular contractility and whether microgravity impacts on circadian clock system. Sprague-Dawley rats were subjected to 28-day hindlimb-unweighting to simulate the effects of microgravity on vasculature. Cerebrovascular contractility was estimated by investigating vasoconstrictor responsiveness and myogenic tone. The circadian regulation of CaV1.2 channel was determined by recording whole-cell currents, evaluating protein and mRNA expressions. Then the candidate miRNA in relation with Ca2+ signal was screened. Lastly, the underlying pathway involved in circadian regulation of cerebrovascular contractility was determined. The major findings of this study are: (1) The clock gene BMAL1 could induce the expression of miR-103, and in turn modulate the circadian regulation of CaV1.2 channel in rat cerebral arteries at post-transcriptional level; and (2) simulated microgravity disrupted intrinsic diurnal oscillation in rat cerebrovascular contractility by altering circadian regulation of BMAL1/miR-103/CaV1.2 signal pathway. View Full-Text
Keywords: simulated microgravity; vascular contractility; L-type CaV1.2 channel; circadian regulation; miRNA simulated microgravity; vascular contractility; L-type CaV1.2 channel; circadian regulation; miRNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Chen, L.; Zhang, B.; Yang, L.; Bai, Y.-G.; Song, J.-B.; Ge, Y.-L.; Ma, H.-Z.; Cheng, J.-H.; Ma, J.; Xie, M.-J. BMAL1 Disrupted Intrinsic Diurnal Oscillation in Rat Cerebrovascular Contractility of Simulated Microgravity Rats by Altering Circadian Regulation of miR-103/CaV1.2 Signal Pathway. Int. J. Mol. Sci. 2019, 20, 3947.

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