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Quinapril treatment abolishes diabetes-associated atherosclerosis in RAGE/apolipoprotein E double knockout mice

Objective/Rationale - Both the renin-angiotensin system (RAS) and the receptor for advanced glycation end products (RAGE) potentiate diabetes-associated atherosclerosis (DAA). We assessed the effectiveness of concomitant RAS and RAGE inhibition on DAA. - Methods - Diabetic (5 × 55 mg/kg streptozotoc...

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Main Authors: Watson, Anna M. D. (Author) , Li, Jiaze (Author) , Samijono, Dian (Author) , Bierhaus, Angelika (Author) , Thomas, Merlin C. (Author) , Jandeleit-Dahm, Karin A. M. (Author) , Cooper, Mark E. (Author)
Format: Article (Journal)
Language:English
Published: 4 June 2014
In: Atherosclerosis
Year: 2014, Volume: 235, Issue: 2, Pages: 444-448
ISSN:1879-1484
DOI:10.1016/j.atherosclerosis.2014.05.945
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.atherosclerosis.2014.05.945
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0021915014012088
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Author Notes:Anna M.D. Watson, Jiaze Li, Dian Samijono, Angelika Bierhaus, Merlin C. Thomas, Karin A.M. Jandeleit-Dahm, Mark E. Cooper
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Summary:Objective/Rationale - Both the renin-angiotensin system (RAS) and the receptor for advanced glycation end products (RAGE) potentiate diabetes-associated atherosclerosis (DAA). We assessed the effectiveness of concomitant RAS and RAGE inhibition on DAA. - Methods - Diabetic (5 × 55 mg/kg streptozotocin daily) and non-diabetic male RAGE/apolipoprotein E double knockout (RAGE/apoE DKO) mice were treated with quinapril (30 mg/kg/day) for 20 weeks. At the end of the study aortic plaques were assessed. - Results - Diabetic RAGE/apoE DKO showed significantly less plaque area than diabetic apoE KO mice. Plaque deposition was almost abolished in quinapril treated diabetic RAGE/apoE DKOs, with significant attenuation of vascular collagen deposition, nitrotyrosine staining, and reduced macrophage infiltration. Expression of the advanced glycation end product receptor 3 (galectin 3) was also significantly reduced. - Conclusion - Concomitant inhibition of RAS and RAGE signalling almost completely inhibited the development of experimental DAA. A dual therapeutic approach may be a superior strategy for the treatment of diabetic macrovascular disease..
Item Description:Gesehen am 27.08.2020
Physical Description:Online Resource
ISSN:1879-1484
DOI:10.1016/j.atherosclerosis.2014.05.945

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