Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents and Equipment
2.2. Animal Model of Coronary Ischemia/Reperfusion
2.3. Echocardiography
2.4. Evans Blue/TTC Staining
2.5. Confocal Microscopy
2.6. Determination of Cardiac TroponinI
2.7. Histology and Immunohistochemistry
2.8. Statistical Analysis
3. Results
3.1. ApTOLL Induces Cardiac Protection in Response to IR
3.2. ApTOLL Reduces Left Ventricle Necrosis and Fibrosis by Day 7 after IR
3.3. APTOLL Inhibits the Expression of MMP-9 by Day 7 after IR
3.4. ApTOLL Reduces the Expression of Pro-Inflammatory Cytokines 7 Days After Reperfusion
4. Discussion
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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PARAMETER | PLACEBO D3 | APTOLL D3 | PLACEBO D7 | APTOLL D7 | PARAMETER |
---|---|---|---|---|---|
IVSD (mm) | 11.68 ± 0.806 | 10.857 ± 0.61 | 10.124 ± 1.357 | 11.353 ± 1.276 | IVSD (mm) |
LVIDD (mm) | 37.96 ± 4.219 | 39.511 ± 4.319 | 38.488 ± 8.667 | 38.067 ± 6.052 | LVIDD (mm) |
LVPWD (mm) | 13.430 ± 2.394 | 9.954 ± 1.746 | 10.475 ± 0.67 | 11.093 ± 2.796 | LVPWD (mm) |
IVSS (mm) | 15.77 ± 2.264 | 13.562 ± 0.932 | 13.153 ± 2.806 | 14.177 ± 1.678 | IVSS (mm) |
LVIDS (mm) | 26.28 ± 4.36 | 29.126 ± 3.493 | 27.316 ± 5.860 | 24.705 ± 4.129 | LVIDS (mm) |
LVPWS (mm) | 15.77 ± 3.383 | 11.024 ± 1.339 | 10.926 ± 1.704 | 11.90 ± 1.722 | LVPWS |
EF (%) | 49.07 ± 5.91 | 46.31 ± 2.60 | 55.14 ± 4.947 | 66.85 ± 3.196 * | EF (%) |
FS (%) | 21.25 ± 3.77 | 20.272 ± 1.443 | 28.55 ± 2.530 | 34.75 ± 2.492 * | FS (%) |
HR (bpm) | 99 ± 31.494 | 111.1O1 ± 27.31 | 103.444 ± 31.269 | 91.875 ± 11.849 | HR (bpm) |
CO (mL/sec) | 3614 ± 2068.651 | 3940.33 ± 1217.115 | 3801.111 ± 1.826 | 3918.875 ± 1356 | CO (mL/sec) |
CYTOKINE | PLACEBO | APTOLL |
---|---|---|
CCL5 | 1.108 ± 0.141 | 0.27 ± 0.070 |
CXCL1 | 0.429 ± 0.024 | 0.105 ± 0.023 |
CXCL10 | 1.542 ± 0.237 | 0.37 ± 0.07 |
G-CSF | 0.372 ± 0.088 | 0.0732 ± 0.014 |
GM-CSF | 0.261 ± 0.057 | 0.031 ± 0.009 |
ICAM-1 | 0.154 ± 0.030 | 0.045 ± 0.009 |
INF-g | 0.092 ± 0.019 | 0 |
IL1-a | 0.255 ± 0.043 | 0.108 ± 0.018 |
ILI-b | 0.616 ± 0.146 | 0.047 ± 0.146 |
IL-IRA | 0.193 ± 0.023 | 0.421 ± 0.123 |
IL2 | 0.493 ± 0.074 | 0.141 ± 0.036 |
IL5 | 0.197 ± 0.020 | 0.014 ± 0.004 |
IL6 | 0.309 ± 0.040 | 0.165 ± 0.043 |
IL8 | 0.317 ± 0.042 | 0.183 ± 0.047 |
IL12 | 0.392 ± 0.054 | 0.213 ± 0.054 |
IL16 | 0.306 ± 0.031 | 0.16 ± 0.046 |
IL17-A | 0.42 ± 0.042 | 0.109 ± 0.032 |
IL18 | 0.311 ± 0.077 | 0.504 ± 0.116 |
IL21 | 0.466 ± 0.074 | 0.159 ± 0.029 |
IL27 | 0.348 ± 0.037 | 0 |
MIF | 1.359 ± 0.200 | 0.527 ± 0.089 |
SERPIN-E1 | 0.876 ± 0.095 | 0.454 ± 0.076 |
TNF-a | 0.52 ± 0.040 | 0.152 ± 0.045 |
TREM-1 | 0.4192 ± 0.039 | 0.105 ± 0.031 |
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Ramirez-Carracedo, R.; Tesoro, L.; Hernandez, I.; Diez-Mata, J.; Piñeiro, D.; Hernandez-Jimenez, M.; Zamorano, J.L.; Zaragoza, C. Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction. Biomolecules 2020, 10, 1167. https://doi.org/10.3390/biom10081167
Ramirez-Carracedo R, Tesoro L, Hernandez I, Diez-Mata J, Piñeiro D, Hernandez-Jimenez M, Zamorano JL, Zaragoza C. Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction. Biomolecules. 2020; 10(8):1167. https://doi.org/10.3390/biom10081167
Chicago/Turabian StyleRamirez-Carracedo, Rafael, Laura Tesoro, Ignacio Hernandez, Javier Diez-Mata, David Piñeiro, Macarena Hernandez-Jimenez, Jose Luis Zamorano, and Carlos Zaragoza. 2020. "Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction" Biomolecules 10, no. 8: 1167. https://doi.org/10.3390/biom10081167