Carvedilol Ameliorates Experimental Atherosclerosis by Regulating Cholesterol Efflux and Exosome Functions
Abstract
:1. Introduction
2. Results
2.1. Treatment with Carvedilol Upregulated ABCA1 Expression and Cholesterol Efflux in Both Human Monocytic (THP-1) and Human Hepatic (Huh-7) Cells
2.2. Increased ABCA1 Expression and Function in Exosomes of Carvedilol-Treated THP-1 Macrophages
2.3. Carvedilol Inhibited Akt and NF-κB Signaling in THP-1 Macrophages
2.4. Treatment with Carvedilol Inhibited Atherosclerosis Progression in Atherosclerosis-Prone ldlr−/− Mice
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Cell Culture
4.3. Measurement of Nonspecific Cytotoxicity of Cav
4.4. Cholesterol Efflux
4.5. Exosome Isolation by Polyethylene Glycol (PEG)
4.6. Semiquantification Analysis of Cell Culture Medium (CCM) Exosomes or Mice Serum Exosomes by Glycan-Recognition Bead, EXÖBead®
4.7. High-Resolution Liquid-Cell Transmission Electron Microscopy (TEM)
4.8. Nanoparticle Tracking Analysis
4.9. Western Blotting
4.10. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR)
4.11. Nuclear Extract Preparation
4.12. Electrophoresis Mobility Shift Assay (EMSA)
4.13. Animals
4.14. Histology, Immunohistochemistry, and Plaque Analyses
4.15. Oil-Red O Staining (ORO)
4.16. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ABCA1 | ATP-binding cassette transporter A1 |
Akt | Protein kinase B |
AP-1 | Activating protein-1 |
CAD | Coronary artery disease |
Cav | Carvedilol |
CCM | Cell culture medium |
ECs | Endothelial cells |
EMSA | Electrophoresis mobility shift assay |
ERK | Extracellular signal-regulated kinase |
HDL | High-density lipoprotein |
Huh-7 | Human hepatic cell line |
IFN | Interferon |
IκB | Inhibitor of kappa B |
JNK | c-Jun N-terminal kinase |
LDH | Lactate dehydrogenase |
LDL | Low-density lipoprotein |
Ldlr−/− | Low-density lipoprotein receptors knockout |
LXR | Liver X receptor |
MAPK | Mitogen-activated protein kinase |
MTT | 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide |
NF-κB | Nuclear factor-kappa B |
ORO | Oil-red O staining |
PPAR | Peroxisome proliferator-activated receptor |
RCT | Reverse cholesterol transport |
SMPDL3A | Sphingomyelin Phosphodiesterase Acid Like 3A |
TEM | Transmission electron microscopy |
THP-1 | Human monocytic cell line |
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Chen, S.-J.; Tsui, P.-F.; Chuang, Y.-P.; Chiang, D.M.-L.; Chen, L.W.; Liu, S.-T.; Lin, F.-Y.; Huang, S.-M.; Lin, S.-H.; Wu, W.-L.; et al. Carvedilol Ameliorates Experimental Atherosclerosis by Regulating Cholesterol Efflux and Exosome Functions. Int. J. Mol. Sci. 2019, 20, 5202. https://doi.org/10.3390/ijms20205202
Chen S-J, Tsui P-F, Chuang Y-P, Chiang DM-L, Chen LW, Liu S-T, Lin F-Y, Huang S-M, Lin S-H, Wu W-L, et al. Carvedilol Ameliorates Experimental Atherosclerosis by Regulating Cholesterol Efflux and Exosome Functions. International Journal of Molecular Sciences. 2019; 20(20):5202. https://doi.org/10.3390/ijms20205202
Chicago/Turabian StyleChen, Sy-Jou, Pi-Fen Tsui, Yi-Ping Chuang, Dapi Meng-Lin Chiang, Liv Weichien Chen, Shu-Ting Liu, Feng-Yen Lin, Shih-Ming Huang, Shih-Hua Lin, Wan-Lin Wu, and et al. 2019. "Carvedilol Ameliorates Experimental Atherosclerosis by Regulating Cholesterol Efflux and Exosome Functions" International Journal of Molecular Sciences 20, no. 20: 5202. https://doi.org/10.3390/ijms20205202