The Anti-Atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin—An Experimental Study
Abstract
:1. Introduction
2. Results
2.1. Body Weight and Biochemical Analysis
2.2. Morphometry, Collagen, and Elastin
2.3. Immunohistochemistry
3. Discussion
4. Materials and Methods
4.1. Animal Model and Experimental Design
- (1)
- Control group (COG): normal saline was administered every day by esophageal gavage to make all interventions comparable between groups.
- (2)
- Bosentan group (BOG): bosentan (Actelion Pharmaceuticals LTD, Allschwil, Switzerland) was administered by esophageal gavage (100 mg/kg/day).
- (3)
- Atorvastatin group (ATG): mice were treated with atorvastatin (20 mg/kg/day) that was administered by esophageal gavage. The detailed protocol has been described in previous publication [8].
- (4)
- Bosentan and atorvastatin (BO + ATG): concomitant bosentan and atorvastatin administration by esophageal gavage, as described previously, for 6 weeks.
4.2. Histological Parameters
4.3. Histomorphometry
4.4. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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COG (n = 12) | BOG (n = 12) | ATG (n = 12) | BO + ATG (n = 12) | p | |
---|---|---|---|---|---|
Weight (g) | 34.4 ± 4.2 | 33.3 ± 4.8 | 32.9 ± 3.9 | 33.5 ± 4.2 | 0.512 |
FPG (mg/dL) | 281 ± 29 | 289 ± 55 | 295 ± 45 | 309 ± 49 | 0.794 |
TC (mg/dL) | 759 ± 131 | 758 ± 182 | 511 ± 131 * | 502 ± 191 * | <0.001 |
TG (mg/dl) | 155 ± 41 | 145 ± 34 | 129 ± 30 | 131 ± 33 | 0.400 |
COG (n = 12) | BOG (n = 12) | ATG (n = 12) | BO + ATG (n = 12) | p | |
---|---|---|---|---|---|
Lumen stenosis (%) | 24.6 ± 4.8 | 19.5 ± 2.2 a,c,d | 12.8 ± 4.8 a,b,d | 9.1 ± 2.7 a,b,c | <0.001 |
Elastin (%) plaque | 8.12 ± 2.10 | 10.62 ± 6.52 c,d | 25.17 ± 6.91 a | 31.02 ± 5.23 a,b | <0.001 |
Collagen (%) plaque | 14.21 ± 4.21 | 22.83 ± 4.79 a,c,d | 31.88 ± 5.97 a,b | 40.33 ± 8.72 a,b,c | <0.001 |
Fibrous cap thickness (μm) | 9.12 ± 3.10 | 13.12 ± 3.23 a,c,d | 23.12 ± 5.44 a,b,d | 48.12 ± 6.21 a,b,c | <0.001 |
a-actin (VSMCs) (%) plaque | 17.13 ± 3.21 | 26.88 ± 6.06 a | 20.53 ± 6.97 | 28.10 ± 6.82 a | 0.005 |
Mac-3 (macrophages) (%) plaque | 34.56 ± 10.25 | 26.46 ± 6.82 a,c,d | 15.09 ± 3.22 a,b,c | 10.12 ± 3.78 a,b,c | <0.001 |
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Stasinopoulou, M.; Kostomitsopoulos, N.; Kadoglou, N.P.E. The Anti-Atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin—An Experimental Study. Int. J. Mol. Sci. 2024, 25, 6614. https://doi.org/10.3390/ijms25126614
Stasinopoulou M, Kostomitsopoulos N, Kadoglou NPE. The Anti-Atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin—An Experimental Study. International Journal of Molecular Sciences. 2024; 25(12):6614. https://doi.org/10.3390/ijms25126614
Chicago/Turabian StyleStasinopoulou, Marianna, Nikolaos Kostomitsopoulos, and Nikolaos P. E. Kadoglou. 2024. "The Anti-Atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin—An Experimental Study" International Journal of Molecular Sciences 25, no. 12: 6614. https://doi.org/10.3390/ijms25126614