ArticleDiabetologia2016
The angiotensin II type 2 receptor agonist Compound 21 is protective in experimental diabetes-associated atherosclerosis.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Protective effects of buloxibutid and empagliflozin on hypertension-induced cardiac and vascular injury in rats.Journal of molecular histology · 2026Article
- Effect of liraglutide on atherosclerosis in patients with impaired glucose tolerance: A double‑blind, randomized controlled clinical trial.Experimental and therapeutic medicine · 2023Article
- Receptor autoantibodies: Associations with cardiac markers, histology, and function in human non-ischaemic heart failure.ESC heart failure · 2023Article
- The Angiotensin ATPharmacological reviews · 2022Review
- Understanding diabetes-induced cardiomyopathy from the perspective of renin angiotensin aldosterone system.Pflugers Archiv : European journal of physiology · 2022Review
- Suppression of Inflammatory Cardiac Cytokine Network in Rats with Untreated Obesity and Pre-Diabetes by AT2 Receptor Agonist NP-6A4.Frontiers in pharmacology · 2021Article
- Combination of C21 and ARBs with rhACE2 as a therapeutic protocol: A new promising approach for treating ARDS in patients with coronavirus infection.Medical journal of the Islamic Republic of Iran · 2020Article
- AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis.Journal of the American Society of Nephrology : JASN · 2019Article
- Emerging Therapy in Hypertension.Current hypertension reports · 2019Review
- Chronic administration of the angiotensin type 2 receptor agonist C21 improves insulin sensitivity in C57BL/6 mice.Physiological reports · 2018Article
- The Effect of a Nonpeptide Angiotensin II Type 2 Receptor Agonist, Compound 21, on Aortic Aneurysm Growth in a Mouse Model of Marfan Syndrome.Journal of cardiovascular pharmacology · 2018Article
- Angiotensin II type 2 receptor inhibits expression and function of insulin receptor in rat renal proximal tubule cells.Journal of the American Society of Hypertension : JASH · 2018Article
- Cell-Specific Protective Signaling Induced by the Novel AT2R-Agonist NP-6A4 on Human Endothelial and Smooth Muscle Cells.Frontiers in pharmacology · 2018Article
- The Selective Angiotensin II Type 2 Receptor Agonist, Compound 21, Attenuates the Progression of Lung Fibrosis and Pulmonary Hypertension in an Experimental Model of Bleomycin-Induced Lung Injury.Frontiers in physiology · 2018Article
- Angiotensin II AT2 Receptors Contribute to Regulate the Sympathoadrenal and Hormonal Reaction to Stress Stimuli.Cellular and molecular neurobiology · 2018Review
- Role of Vitamin D in Cardiovascular Diseases.Endocrinology and metabolism clinics of North America · 2017Review
- Oxidative Stress in Human Atherothrombosis: Sources, Markers and Therapeutic Targets.International journal of molecular sciences · 2017Review
- Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium.Scientific reports · 2017Article
- Sex and gender differences in hypertensive kidney injury.American journal of physiology. Renal physiology · 2017Review
- Conflicting mechanisms of AT2 cardioprotection revealed.Cardiovascular research · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisAngiotensin II is well-recognised to be a key mediator in driving the pathological events of diabetes-associated atherosclerosis via signalling through its angiotensin II type 1 receptor (AT1R) subtype. However, its actions via the angiotensin II type 2 receptor (AT2R) subtype are still poorly understood. This study is the first to investigate the role of the novel selective AT2R agonist, Compound 21 (C21) in an experimental model of diabetes-associated atherosclerosis (DAA).
methodsStreptozotocin-induced diabetic Apoe-knockout mice were treated with vehicle (0.1 mol/l citrate buffer), C21 (1 mg/kg per day), candesartan cilexetil (4 mg/kg per day) or C21 + candesartan cilexetil over a 20 week period. In vitro models of DAA using human aortic endothelial cells and monocyte cultures treated with C21 were also performed. At the end of the experiments, assessment of plaque content and markers of oxidative stress, inflammation and fibrosis were conducted.
resultsC21 treatment significantly attenuated aortic plaque deposition in a mouse model of DAA in vivo, in association with a decreased infiltration of macrophages and mediators of inflammation, oxidative stress and fibrosis. On the other hand, combination therapy with C21 and candesartan (AT1R antagonist) appeared to have a limited additive effect in attenuating the pathology of DAA when compared with either treatment alone. Similarly, C21 was found to confer profound anti-atherosclerotic actions at the in vitro level, particularly in the setting of hyperglycaemia. Strikingly, these atheroprotective actions of C21 were completely blocked by the AT2R antagonist PD123319. CONCLUSIONS/
interpretationTaken together, these findings provide novel mechanistic and potential therapeutic insights into C21 as a monotherapy agent against DAA.
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