The Anti-Atherosclerosis Effect of Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, in Apolipoprotein E Knockout Mice
Abstract
:1. Introduction
2. Results
2.1. Focus on Atherosclerosis
2.1.1. Anakinra Reduces the Atherosclerotic Plaque Area in ApoE–/– Mice
2.1.2. The Dose-Dependent Effect of Anakinra on the Activation of the NLRP3 Inflammasome and Upregulated Expression of Inflammatory Adhesion Molecules in Human Umbilical Vein Endothelial Cells (HUVECs)
2.1.3. The Dose-Dependent Effect of Anakinra on the Activated Nlrp3 Inflammasome and Upregulated Expression of Angiogenesis Molecules in Rat Aortic Smooth Muscle Cells (RAOSMCs)
2.1.4. The Effect of Anakinra on the p38 Mitogen-Activated Protein Kinase (MAPK)/Nuclear Factor-κB (NF-κB) Pathway in RAOSMCs and HUVECs
2.1.5. Anakinra Inhibits Migration of RAOSMCs
2.2. Focus on Fat
2.2.1. Immunofluorescent Staining of CD68 and Hematoxylin and Eosin (H&E) Staining in Visceral Adipose Tissue
2.2.2. The Dose-Dependent Effect of Anakinra on the Activated NLRP3 Inflammasome and Upregulated Expression of Inflammatory Molecules in 3T3-L1 Adipocytes
2.2.3. Expression of Phosphorylated c-Jun N-Terminal Kinase (p-JNK), p-p38, and p-ERK in the Liver and Visceral Fat Tissue
3. Discussion
4. Materials and Methods
4.1. Animals, Diet, and Treatment Protocols
4.2. Immunofluorescent Staining of CD68 and H&E Staining in the Adipose Tissue
4.3. THP-1-Conditioned Media and Induction of NLRP3 Inflammasome Expression in HUVECs, RAOSMCs, and 3T3-L1 Cells
4.4. Reverse Transcription–Quantitative Polymerase Chain Reaction (RT–qPCR)
4.5. Western Blot Analysis
4.6. RAOSMC Migration Assays
4.7. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations and Acronyms
ANOVA | Analysis of variance |
ApoE–/– | Apolipoprotein E knockout |
CRP | C-reactive protein |
CVD | Cardiovascular disease |
ERK | Extracellular-regulated kinase |
H&E | Hematoxylin and eosin |
HUVEC | Human umbilical vein endothelial cell |
ICAM | Intracellular adhesion molecule |
IL | Interleukin |
LDL-C | Low-density lipoprotein cholesterol |
LPS | Lipopolysaccharide |
MAPK | Mitogen-activated protein kinase |
MCP-1 | Monocyte chemoattractant protein-1 |
MI | Myocardial infarction |
MMP-9 | Matrix metalloproteinase-9 |
NF-κB | Nuclear factor kappa-light-chain-enhancer of activated B cell |
NLRP3 | NACHT, LRR, and PYD domain-containing protein 3 |
PDGF | Platelet-derived growth factor |
P-JNK | Phosphorylated c-Jun N-terminal kinase |
RAOSMC | Rat aortic smooth muscle cell |
SMA | Smooth muscle actin |
TG | Triglycerides |
TNF-α | Tumor necrosis factor-α. |
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Ku, E.J.; Kim, B.-R.; Lee, J.-I.; Lee, Y.K.; Oh, T.J.; Jang, H.C.; Choi, S.H. The Anti-Atherosclerosis Effect of Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, in Apolipoprotein E Knockout Mice. Int. J. Mol. Sci. 2022, 23, 4906. https://doi.org/10.3390/ijms23094906
Ku EJ, Kim B-R, Lee J-I, Lee YK, Oh TJ, Jang HC, Choi SH. The Anti-Atherosclerosis Effect of Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, in Apolipoprotein E Knockout Mice. International Journal of Molecular Sciences. 2022; 23(9):4906. https://doi.org/10.3390/ijms23094906
Chicago/Turabian StyleKu, Eu Jeong, Bo-Rahm Kim, Jee-In Lee, Yun Kyung Lee, Tae Jung Oh, Hak C. Jang, and Sung Hee Choi. 2022. "The Anti-Atherosclerosis Effect of Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, in Apolipoprotein E Knockout Mice" International Journal of Molecular Sciences 23, no. 9: 4906. https://doi.org/10.3390/ijms23094906