ArticleDiabetologia2010
Angiotensin II subtype 2 receptor blockade and deficiency attenuate the development of atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes.
Article in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 38 citations in OpenAlex.
- Cardiometabolic traits mediating the effect of education on the risk of DKD and CKD: a Mendelian randomization study.Frontiers in nutrition · 2024Article
- The Angiotensin ATPharmacological reviews · 2022Review
- Effect ofFrontiers in endocrinology · 2022Article
- Construction of an immune-related signature for predicting the ischemic events in patients undergoing carotid endarterectomy.Frontiers in genetics · 2022Article
- Glucose and Blood Pressure-Dependent Pathways-The Progression of Diabetic Kidney Disease.International journal of molecular sciences · 2020Review
- Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes.BMC cardiovascular disorders · 2016Article
- The angiotensin II type 2 receptor agonist Compound 21 is protective in experimental diabetes-associated atherosclerosis.Diabetologia · 2016Article
- Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2016Article
- The pathobiology of diabetic vascular complications--cardiovascular and kidney disease.Journal of molecular medicine (Berlin, Germany) · 2014Review
- Effects of angiotensin-converting enzyme inhibitor, captopril, on bone of mice with streptozotocin-induced type 1 diabetes.Journal of bone and mineral metabolism · 2014Article
- Opposite effects of angiotensins receptors type 2 and type 4 on streptozotocin induced diabetes vascular alterations in mice.Cardiovascular diabetology · 2014Article
- PD123319 augments angiotensin II-induced abdominal aortic aneurysms through an AT2 receptor-independent mechanism.PloS one · 2013Article
- Comparative effects of different modes of renin angiotensin system inhibition on hypercholesterolaemia-induced atherosclerosis.British journal of pharmacology · 2012Article
- LOX-1 and angiotensin receptors, and their interplay.Cardiovascular drugs and therapy · 2011Review
- Delayed intervention with AGE inhibitors attenuates the progression of diabetes-accelerated atherosclerosis in diabetic apolipoprotein E knockout mice.Diabetologia · 2011Article
- Genetic variants of the Renin Angiotensin system: effects on atherosclerosis in experimental models and humans.Current atherosclerosis reports · 2010Review
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
aims/hypothesisMost 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 (AT(2)R) may modulate key processes linked to atherosclerosis. The aim of this study was to investigate the role of AT(2)R in diabetes-associated atherosclerosis using pharmacological blockade and genetic deficiency.
methodsAortic 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 AT(2)R antagonist PD123319 (5 mg kg(-1) day(-1)) via osmotic minipump for 20 weeks (n = 7-8 per group).
resultsDiabetes 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 < 0.001) as well as a significant increase in aortic expression of the gene At ( 2 ) r (also known as Agtr2). The increase in plaque area with diabetes was attenuated in AT(2)R antagonist-treated diabetic Apoe-KO mice (7.1 +/- 0.5%, p < 0.05) and in diabetic At ( 2 ) r/Apoe DKO mice (9.2 +/- 1.3%, p < 0.05). These benefits occurred independently of glycaemic control or BP, and were associated with downregulation of a range of pro-inflammatory cytokines, adhesion molecules, chemokines and various extracellular matrix proteins. CONCLUSIONS/
interpretationThis study provides evidence for AT(2)R playing a role in the development of diabetes-associated atherosclerosis. These findings suggest a potential utility of AT(2)R blockers in the prevention and treatment of diabetic macrovascular complications.
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