Angiotensin II subtype 2 receptor blockade and deficiency attenuate the development of atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes

Aims/hypothesis Most of the known actions of angiotensin II have been considered primarily to be the result of angiotensin II subtype 1 receptor activation. However, recent data suggest that the angiotensin II subtype 2 receptor (AT₂R) may modulate key processes linked to atherosclerosis. The aim of this study was to investigate the role of AT₂R in diabetes-associated atherosclerosis using pharmacological blockade and genetic deficiency. Methods Aortic plaque deposition was assessed in streptozotocin-induced diabetic apolipoprotein E (Apoe) knockout (KO) and At ₂ r (also known as Agtr2)/Apoe double-KO (DKO) mice. Control and diabetic Apoe-KO mice received an AT₂R antagonist PD123319 (5 mg kg⁻¹ day⁻¹) via osmotic minipump for 20 weeks (n = 7-8 per group). Results Diabetes was associated with a sixfold increase in plaque area (diabetic Apoe-KO: 12.7 ± 1.4% vs control Apoe-KO: 2.3 ± 0.4%, p