Version 1
: Received: 13 May 2024 / Approved: 14 May 2024 / Online: 14 May 2024 (06:50:40 CEST)
How to cite:
Stasinopoulou, M.; Kostomitsopoulos, N.; Kadoglou, N. P. The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study. Preprints2024, 2024050913. https://doi.org/10.20944/preprints202405.0913.v1
Stasinopoulou, M.; Kostomitsopoulos, N.; Kadoglou, N. P. The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study. Preprints 2024, 2024050913. https://doi.org/10.20944/preprints202405.0913.v1
Stasinopoulou, M.; Kostomitsopoulos, N.; Kadoglou, N. P. The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study. Preprints2024, 2024050913. https://doi.org/10.20944/preprints202405.0913.v1
APA Style
Stasinopoulou, M., Kostomitsopoulos, N., & Kadoglou, N. P. (2024). The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study. Preprints. https://doi.org/10.20944/preprints202405.0913.v1
Chicago/Turabian Style
Stasinopoulou, M., Nikolaos Kostomitsopoulos and Nikolaos P.E. Kadoglou. 2024 "The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study" Preprints. https://doi.org/10.20944/preprints202405.0913.v1
Abstract
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 4 groups: 1) Control/COG: no intervention. 2) ΒΟG: bosentan 100 mg/kg/day per os. 3) ATG: atorvastatin 20mg/kg/day per os). 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 concentrations were determined. The percentage of lumen stenosis significantly decreased across all treated groups: BOG: 19.5±2.2%, ATG: 12.8±4.8%, BO+ATG: 9.1±2.7% compared to controls (24.6±4.8%, p<0.001). Both atorvastatin and bosentan significantly increased collagen content and fibrous cap thickness versus COG (p<0.01). All intervention groups reduced the relative intra-plaque concentrations of MCP-1, MMP-3,-9, and increased TIMP-1 compared to COG (p<0.001). Importantly, bosentan showed modest but additive to atorvastatin effects on the latter parameters compared COG (p<0.05). Bosentan treatment in diabetic, atherosclerotic apoE-/- mice delayed the atherosclerosis progression and enhanced plaques’ stability, showing modest but complementary effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.
Medicine and Pharmacology, Cardiac and Cardiovascular Systems
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
