Astaxanthin Counteracts Vascular Calcification In Vitro Through an Early Up-Regulation of SOD2 Based on a Transcriptomic Approach
| العنوان: | Astaxanthin Counteracts Vascular Calcification In Vitro Through an Early Up-Regulation of SOD2 Based on a Transcriptomic Approach |
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| المؤلفون: | You-Tien Tsai, Huei-Wen Chen, Jenq-Wen Huang, Hsiang-Yuan Yeh, Min-Tser Liao, Tzu-Hang Yuan, Chia-Ter Chao |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 21, Iss 8530, p 8530 (2020) Volume 21 Issue 22 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Vascular smooth muscle, senescence, 030204 cardiovascular system & hematology, Xanthophylls, medicine.disease_cause, Antioxidants, Muscle, Smooth, Vascular, lcsh:Chemistry, chemistry.chemical_compound, 0302 clinical medicine, Protein Interaction Mapping, oxidative stress, vascular smooth muscle cells, lcsh:QH301-705.5, Spectroscopy, Aorta, Cells, Cultured, Oligonucleotide Array Sequence Analysis, chemistry.chemical_classification, reactive oxygen species, Gene knockdown, Calcinosis, General Medicine, Computer Science Applications, Up-Regulation, astaxanthin, Phenotype, Senescence, Myocytes, Smooth Muscle, SOD2, Biology, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Fibrinolytic Agents, Astaxanthin, medicine, Animals, Humans, chronic kidney disease-mineral bone disorder, Physical and Theoretical Chemistry, Vascular Calcification, Molecular Biology, Reactive oxygen species, Superoxide Dismutase, Organic Chemistry, Computational Biology, aortic calcification, medicine.disease, Rats, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, chemistry, Cancer research, RNA, Transcriptome, Oxidative stress, chronic kidney disease, Calcification |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f9adc24bb9751608523bb7d5036724b https://pubmed.ncbi.nlm.nih.gov/33198315 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4f9adc24bb9751608523bb7d5036724b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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