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

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Abstract

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?55mg/kg streptozotocin daily) and non-diabetic male RAGE/apolipoprotein E double knockout (RAGE/apoE DKO) mice were treated with quinapril (30mg/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.
Original languageEnglish
Pages (from-to)444 - 448
Number of pages5
JournalAtherosclerosis
Volume235
Issue number2
DOIs
Publication statusPublished - 2014

Cite this

@article{5fd3900d1300442388fbc168d7df190b,
title = "Quinapril treatment abolishes diabetes-associated atherosclerosis in RAGE/apolipoprotein E double knockout mice",
abstract = "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?55mg/kg streptozotocin daily) and non-diabetic male RAGE/apolipoprotein E double knockout (RAGE/apoE DKO) mice were treated with quinapril (30mg/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.",
author = "Watson, {Anna M D} and Jiaze Li and D Samijono and Angelika Bierhaus and Thomas, {Merlin Christopher} and Jandeleit-Dahm, {Karin Agnes Maria} and Cooper, {Mark Emmanuel}",
year = "2014",
doi = "10.1016/j.atherosclerosis.2014.05.945",
language = "English",
volume = "235",
pages = "444 -- 448",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier",
number = "2",

}

Quinapril treatment abolishes diabetes-associated atherosclerosis in RAGE/apolipoprotein E double knockout mice. / Watson, Anna M D; Li, Jiaze; Samijono, D; Bierhaus, Angelika; Thomas, Merlin Christopher; Jandeleit-Dahm, Karin Agnes Maria; Cooper, Mark Emmanuel.

In: Atherosclerosis, Vol. 235, No. 2, 2014, p. 444 - 448.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Quinapril treatment abolishes diabetes-associated atherosclerosis in RAGE/apolipoprotein E double knockout mice

AU - Watson, Anna M D

AU - Li, Jiaze

AU - Samijono, D

AU - Bierhaus, Angelika

AU - Thomas, Merlin Christopher

AU - Jandeleit-Dahm, Karin Agnes Maria

AU - Cooper, Mark Emmanuel

PY - 2014

Y1 - 2014

N2 - 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?55mg/kg streptozotocin daily) and non-diabetic male RAGE/apolipoprotein E double knockout (RAGE/apoE DKO) mice were treated with quinapril (30mg/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.

AB - 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?55mg/kg streptozotocin daily) and non-diabetic male RAGE/apolipoprotein E double knockout (RAGE/apoE DKO) mice were treated with quinapril (30mg/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.

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U2 - 10.1016/j.atherosclerosis.2014.05.945

DO - 10.1016/j.atherosclerosis.2014.05.945

M3 - Article

VL - 235

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JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 2

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