Astaxanthin counteracts vascular calcification in vitro through an early up-regulation of SOD2 based on a transcriptomic approach
Journal
International Journal of Molecular Sciences
Journal Volume
21
Journal Issue
22
Pages
1-14
Date Issued
2020
Author(s)
Abstract
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. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
alkaline phosphatase; astaxanthin; bone morphogenetic protein 2; mammalian target of rapamycin; manganese superoxide dismutase; protein akt 3; protein kinase B beta; protein serine threonine kinase; Rac1 protein; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate oxidase 1; Smad4 protein; Smad6 protein; stress activated protein kinase 1; transcription factor RUNX2; unclassified drug; antioxidant; astaxanthin; fibrinolytic agent; manganese superoxide dismutase; reactive oxygen metabolite; RNA; superoxide dismutase; transcriptome; xanthophyll; adcy6 gene; animal cell; Article; blood vessel calcification; cell aging; comparative study; disease course; disease severity; drug activity; drug efficacy; ehmt1 gene; gene; gene expression; gene knockdown; in vitro study; irs1 gene; nonhuman; oxidative stress; pathogenesis; prkaa2 gene; prkag2 gene; protein expression; protein protein interaction; qualitative analysis; quantitative analysis; rat; sesn1 gene; transcriptomics; upregulation; vascular smooth muscle cell; animal; aorta; biology; blood vessel calcification; calcinosis; cell culture; cytology; DNA microarray; human; metabolism; phenotype; protein analysis; smooth muscle cell; upregulation; vascular smooth muscle; Animals; Antioxidants; Aorta; Calcinosis; Cells, Cultured; Computational Biology; Fibrinolytic Agents; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Oligonucleotide Array Sequence Analysis; Oxidative Stress; Phenotype; Protein Interaction Mapping; Rats; Reactive Oxygen Species; RNA; Superoxide Dismutase; Transcriptome; Up-Regulation; Vascular Calcification; Xanthophylls
Publisher
MDPI AG
Type
journal article