The Complementary Effects of Dabigatran Etexilate and Exercise Training on the Development and Stability of the Atherosclerotic Lesions in Diabetic ApoE Knockout Mice.

Autor: Kadoglou NP; Medical School, University of Cyprus, Aglatzia CY 2029, Cyprus., Stasinopoulou M; Center of Experimental Surgery, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece., Gkougkoudi E; Medical School, University of Cyprus, Aglatzia CY 2029, Cyprus., Christodoulou E; Laboratory of Biopharmaceutics & Pharmacokinetics, Department of Pharmacy, School of Health Sciences, National & Kapodistrian University of Athens, 15771 Athens, Greece., Kostomitsopoulos N; Center of Experimental Surgery, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece., Valsami G; Laboratory of Biopharmaceutics & Pharmacokinetics, Department of Pharmacy, School of Health Sciences, National & Kapodistrian University of Athens, 15771 Athens, Greece.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Oct 02; Vol. 16 (10). Date of Electronic Publication: 2023 Oct 02.
DOI: 10.3390/ph16101396
Abstrakt: Aim: To determine the complementary effects of dabigatran etexilate (DE), exercise training (ET), and combination (DE + ET) on the development and stability of the atherosclerotic lesions in diabetic apoE knockout (apoE -/- ) mice. Methods: In 48 male apoE -/- diabetic mice, streptozotocin (STZ) was induced for 5 consecutive days. Mice received a high-fat diet (HFD) for 8 weeks and then were randomized into four groups (1. Control/CG, 2. DEG: HFD with DE, 3. ETG: ET on treadmill, 4. DE + ETG: combination DE and ET treatment). At the end of the eighth week, all mice were euthanatized and morphometry of the aortic lesions at the level of aortic valve was obtained. Collagen, elastin, MCP-1, TNF-a, matrix metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations within plaques at the aortic valve were determined. Results: All active groups had significantly smaller aorta stenosis (DEG:7.9 ± 2.2%, ETG:17.3 ± 5.3%, DE + ETG:7.1 ± 2.7%) compared to CG (23.3 ± 5.5% p < 0.05), reduced the relative intra-plaque content of MCP-1, macrophages, MMP-3, and MMP-9, and considerably increased collagen, elastin, and TIMP-1 ( p < 0.05). Group 4 showed the most pronounced results ( p < 0.05). Both DEG and DE + ETG significantly reduced MMP-2 and TNF-a concentrations compared to ETG and CG ( p < 0.010). Conclusion: DE and ET treatment of diabetic apoE -/- mice resulted in complementary amelioration of atherosclerotic lesions development and stability, mediated by the anti-inflammatory modulation of both DE and ET.
Databáze: MEDLINE
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