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Article

Astaxanthin Counteracts Vascular Calcification In Vitro Through an Early Up-Regulation of SOD2 Based on a Transcriptomic Approach

1
Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital BeiHu Branch, Taipei 10845, Taiwan
2
Geriatric and Community Medicine Research Center, National Taiwan University Hospital BeiHu Branch, Taipei 10845, Taiwan
3
Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei 100233, Taiwan
4
School of Big Data Management, Soochow University, Taipei 11102, Taiwan
5
Genome and Systems Biology Degree Program, Academia Sinica, Taipei 11529, Taiwan
6
Department of Pediatrics, Armed Force Taoyuan General Hospital, Taoyuan County 32551, Taiwan
7
Nephrology division, Department of Internal Medicine, National Taiwan University Hospital YunLin Branch, YunLin County 640203, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8530; https://doi.org/10.3390/ijms21228530
Received: 21 October 2020 / Revised: 30 October 2020 / Accepted: 9 November 2020 / Published: 12 November 2020
Vascular calcification (VC) is a critical contributor to the rising cardiovascular risk among at-risk populations such as those with diabetes or renal failure. The pathogenesis of VC involves an uprising of oxidative stress, for which antioxidants can be theoretically effective. However, astaxanthin, a potent antioxidant, has not been tested before for the purpose of managing VC. To answer this question, we tested the efficacy of astaxanthin against VC using the high phosphate (HP)-induced vascular smooth muscle cell (VSMC) calcification model. RNAs from treated groups underwent Affymetrix microarray screening, with intra-group consistency and inter-group differential expressions identified. Candidate hub genes were selected, followed by validation in experimental models and functional characterization. We showed that HP induced progressive calcification among treated VSMCs, while astaxanthin dose-responsively and time-dependently ameliorated calcification severities. Transcriptomic profiling revealed that 3491 genes exhibited significant early changes during VC progression, among which 26 potential hub genes were selected based on closeness ranking and biologic plausibility. SOD2 was validated in the VSMC model, shown to drive the deactivation of cellular senescence and enhance antioxidative defenses. Astaxanthin did not alter intracellular reactive oxygen species (ROS) levels without HP, but significantly lowered ROS production in HP-treated VSMCs. SOD2 knockdown prominently abolished the anti-calcification effect of astaxanthin on HP-treated VSMCs, lending support to our findings. In conclusion, we demonstrated for the first time that astaxanthin could be a potential candidate treatment for VC, through inducing the up-regulation of SOD2 early during calcification progression and potentially suppressing vascular senescence. View Full-Text
Keywords: astaxanthin; aortic calcification; chronic kidney disease; chronic kidney disease-mineral bone disorder; oxidative stress; reactive oxygen species; senescence; vascular calcification; vascular smooth muscle cells astaxanthin; aortic calcification; chronic kidney disease; chronic kidney disease-mineral bone disorder; oxidative stress; reactive oxygen species; senescence; vascular calcification; vascular smooth muscle cells
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MDPI and ACS Style

Chao, C.-T.; Yeh, H.-Y.; Tsai, Y.-T.; Yuan, T.-H.; Liao, M.-T.; Huang, J.-W.; Chen, H.-W. Astaxanthin Counteracts Vascular Calcification In Vitro Through an Early Up-Regulation of SOD2 Based on a Transcriptomic Approach. Int. J. Mol. Sci. 2020, 21, 8530. https://doi.org/10.3390/ijms21228530

AMA Style

Chao C-T, Yeh H-Y, Tsai Y-T, Yuan T-H, Liao M-T, Huang J-W, Chen H-W. Astaxanthin Counteracts Vascular Calcification In Vitro Through an Early Up-Regulation of SOD2 Based on a Transcriptomic Approach. International Journal of Molecular Sciences. 2020; 21(22):8530. https://doi.org/10.3390/ijms21228530

Chicago/Turabian Style

Chao, Chia-Ter, Hsiang-Yuan Yeh, You-Tien Tsai, Tzu-Hang Yuan, Min-Tser Liao, Jenq-Wen Huang, and Huei-Wen Chen. 2020. "Astaxanthin Counteracts Vascular Calcification In Vitro Through an Early Up-Regulation of SOD2 Based on a Transcriptomic Approach" International Journal of Molecular Sciences 21, no. 22: 8530. https://doi.org/10.3390/ijms21228530

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