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

Autor: You-Tien Tsai, Huei-Wen Chen, Jenq-Wen Huang, Hsiang-Yuan Yeh, Min-Tser Liao, Tzu-Hang Yuan, Chia-Ter Chao
Rok vydání: 2020
Předmět:
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
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 8530, p 8530 (2020)
Volume 21
Issue 22
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje