| Autor: |
Stasinopoulou M; Center of Clinical, Experimental Surgery, and Translational Research, Biomedical Research Foundation, Academy of Athens, 115 27 Athens, Greece., Kostomitsopoulos N; Center of Clinical, Experimental Surgery, and Translational Research, Biomedical Research Foundation, Academy of Athens, 115 27 Athens, Greece., Kadoglou NPE; Medical School, University of Cyprus, 2029 Nicosia, Cyprus. |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of molecular sciences [Int J Mol Sci] 2024 Jun 16; Vol. 25 (12). Date of Electronic Publication: 2024 Jun 16. |
| DOI: |
10.3390/ijms25126614 |
| Abstrakt: |
Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male ApoE - / - mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin, and mice were randomized into four groups: (1) control/COG: no intervention; (2) ΒOG: bosentan 100 mg/kg/day per os; (3) ATG: atorvastatin 20 mg/kg/day per os; and (4) BO + ATG: combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix metalloproteinases (MMP-2, -3, -9), and TIMP-1 were determined. The percentage of lumen stenosis was significantly lower across all treated groups: BOG: 19.5 ± 2.2%, ATG: 12.8 ± 4.8%, and BO + ATG: 9.1 ± 2.7% compared to controls (24.6 ± 4.8%, p < 0.001). The administration of both atorvastatin and bosentan resulted in significantly higher collagen content and thicker fibrous cap versus COG ( p < 0.01). All intervention groups showed lower relative intra-plaque concentrations of MCP-1, MMP-3, and MMP-9 and a higher TIMP-1concentration compared to COG ( p < 0.001). Importantly, latter parameters presented lower levels when bosentan was combined with atorvastatin compared to COG ( p < 0.05). Bosentan treatment in diabetic, atherosclerotic ApoE - / - mice delayed the atherosclerosis progression and enhanced plaques' stability, showing modest but additive effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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