Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Nikolaos PE Kadoglou
* ORCID logo ,
Marianna Stasinopoulou
,
Evangelia Gkougkoudi
,
Eirini Christodoulou
,
Nikolaos Kostomitsopoulos
ORCID logo ,
Georgia Valsami
ORCID logo
Version 1 : Received: 19 September 2023 / Approved: 20 September 2023 / Online: 21 September 2023 (07:36:12 CEST)

A peer-reviewed article of this Preprint also exists.

Kadoglou, N.P.; Stasinopoulou, M.; Gkougkoudi, E.; Christodoulou, E.; Kostomitsopoulos, N.; Valsami, G. The Complementary Effects of Dabigatran Etexilate and Exercise Training on the Development and Stability of the Atherosclerotic Lesions in Diabetic ApoE Knockout Mice. Pharmaceuticals 2023, 16, 1396. Kadoglou, N.P.; Stasinopoulou, M.; Gkougkoudi, E.; Christodoulou, E.; Kostomitsopoulos, N.; Valsami, G. The Complementary Effects of Dabigatran Etexilate and Exercise Training on the Development and Stability of the Atherosclerotic Lesions in Diabetic ApoE Knockout Mice. Pharmaceuticals 2023, 16, 1396.

Abstract

Aim: Complementary effects of dabigatran etexilate (DE), exercise training (ET) and combination (DE+ET) on the development and composition 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 figh-fat diet (HFD) for 8 weeks and were randomized into 4 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 8th week, all mice were euthanatized and morphometry of the aortic lesions at the level of aortic valve was obtained. Collagen, elastin, TNF-a, MCP-1, matrix-metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentration within plaques at 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 concentrations of macrophages, MCP-1, 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 in diabetic apoE-/- mice showed complementary amelioration of atherosclerotic lesions development and stability, mediated by the anti-inflammatory modulation of both DE and ET.

Keywords

dabigatran etexilate; exercise training; atherosclerosis; plaque stability; matrix metalloproteinases; inflammation

Subject

Biology and Life Sciences, Life Sciences

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.

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