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.
|Pages (from-to)||444 - 448|
|Number of pages||5|
|Publication status||Published - 2014|
Watson, A. M. D., Li, J., Samijono, D., Bierhaus, A., Thomas, M. C., Jandeleit-Dahm, K. A. M., & Cooper, M. E. (2014). Quinapril treatment abolishes diabetes-associated atherosclerosis in RAGE/apolipoprotein E double knockout mice. Atherosclerosis, 235(2), 444 - 448. https://doi.org/10.1016/j.atherosclerosis.2014.05.945