Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis
Abstract
:1. Introduction
2. Results
2.1. Increased Expression of Gal-3 in AAA
2.2. Gal-3 Modulated Inflammatory Regulators in Macrophages
2.3. Gal-3 Promoted Up-Regulation of MCP-1 to Enhance the Chemotaxis of Monocytes
2.4. Inhibited Gal-3 Attenuated Macrophage-Induced Death of SMCs
2.5. Resistance of Gal-3 to Macrophage-Induced SMC Apoptosis Associated With Fas Deactivation
3. Discussion
4. Materials and Methods
4.1. Patient Recruitment and Blood Sample Collection
4.2. Enzyme-Linked Immunosorbent Assay
4.3. Animal Aortic Collection
4.4. Histological and Immunohistochemistical Staining
4.5. RNA Interference of Gal-3 Using Small-Interfering RNA
4.6. Cell Lines and Cell Culture
4.7. Chemotaxis Assay
4.8. Gelatin Zymography
4.9. Quantitative Real-Time Polymerase Chain Reaction
4.10. Western Blotting
4.11. Terminal Deoxynucleotidyl Transferase dUTP Nick end Labeling Staining
4.12. Flow Cytometry
4.13. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AAA | Abdominal Aortic Aneurysm |
SMC | Smooth Muscle Cell |
MMP | Matrix Metalloproteinase |
CREB | cAMP-response element binding protein |
NF-κB | Nuclear factor-κB |
CCL5 | C-C motif chemokine 5 |
STAT3 | Signal Transducer and Activator of Transcription 3 |
EDTA | Ethylene-Diamine-Tetra-Acetic Acid |
LPS | Lipopolysaccharide |
IFN-γ | Interferon-gamma |
MCP-1 | Monocyte Chemoattractant Protein-1 |
CM | Conditioned Media |
IL | Interleukin |
TNF-α | Tumor Necrosis Factor-alpha |
GAPDH | Glyceraldehyde 3-phosphate Dehydrogenase |
TUNEL | Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling |
RT-PCR | Reverse Transcription Polymerase Chain Reaction |
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Total No. | CTL | AAA | p Value |
---|---|---|---|
97 | 76 | ||
Aortic diameter (mm) | 20.1 ± 1.7 | 61.4 ± 10.8 | <0.0001 |
Age, yr | 70.5 ± 10.3 | 78.8 ± 8.6 | 0.007 |
Sex (male/female) | 46/51 | 66/10 | <0.001 |
Body weight, kg | 66.3 ± 11.8 | 64.4 ± 12.6 | 0.659 |
Height, cm | 160.4 ± 9.0 | 163.3 ± 7.9 | 0.226 |
Hypertension (%yes) | 86.6 | 75.0 | 0.075 |
Smoke (%yes) | 15.5 | 61.8 | <0.001 |
Hypercholesterolemia (%yes) | 50.5 | 27.6 | 0.003 |
DM (%yes) | 31.9 | 17.1 | 0.034 |
Peripheral vascular disease(%yes) | 1.0 | 4.0 | 0.321 |
COPD (%yes) | 4.1 | 19.7 | 0.001 |
Medications: | |||
ACEi/ARB (%yes) | 65.0 | 48.7 | 0.043 |
Statin (%yes) | 42.3 | 25 | 0.024 |
β-blocker (%yes) | 30.9 | 39.5 | 0.263 |
calcium channel blocker (%yes) | 44.3 | 55.3 | 0.170 |
Aspirin (%yes) | 8.2 | 17.1 | 0.101 |
anti-coagulants (%yes) | 5.2 | 2.6 | 0.468 |
Antiplatelets (%yes) | 6.2 | 31.6 | <0.001 |
Variables | OR (95% CI) | p Value |
---|---|---|
Model 0 | 1.106 (1.062−1.151) | 0.000 |
Model 1 | 1.026 (1.015−1.037) | 0.000 |
Model 2 | 1.104 (1.057−1.152) | 0.000 |
Model 3 | 1.018 (1.009−1.027) | 0.000 |
Model 4 | 1.017 (1.009−1.025) | 0.000 |
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Lu, H.-Y.; Shih, C.-M.; Huang, C.-Y.; Wu, A.T.H.; Cheng, T.-M.; Mi, F.-L.; Shih, C.-C. Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis. Int. J. Mol. Sci. 2020, 21, 8257. https://doi.org/10.3390/ijms21218257
Lu H-Y, Shih C-M, Huang C-Y, Wu ATH, Cheng T-M, Mi F-L, Shih C-C. Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis. International Journal of Molecular Sciences. 2020; 21(21):8257. https://doi.org/10.3390/ijms21218257
Chicago/Turabian StyleLu, Hsin-Ying, Chun-Ming Shih, Chun-Yang Huang, Alexander T. H. Wu, Tsai-Mu Cheng, Fwu-Long Mi, and Chun-Che Shih. 2020. "Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis" International Journal of Molecular Sciences 21, no. 21: 8257. https://doi.org/10.3390/ijms21218257