ArticleRegulatory peptides2012
Oral administration of an angiotensin-converting enzyme 2 activator ameliorates diabetes-induced cardiac dysfunction.
Article in Regulatory peptides, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 73 citations in OpenAlex.
- Novel insights into the central protective role of ACE2 in diabetic cardiomyopathy: from underlying signaling pathways to therapeutic perspectives.Molecular and cellular biochemistry · 2025Review
- The evolution of small molecule enzyme activators.RSC medicinal chemistry · 2023Review
- The systemic and hepatic alternative renin-angiotensin system is activated in liver cirrhosis, linked to endothelial dysfunction and inflammation.Scientific reports · 2023Article
- Recombinant human angiotensin-converting enzyme 2 plays a protective role in mice with sepsis-induced cardiac dysfunction through multiple signaling pathways dependent on converting angiotensin II to angiotensin 1-7.Annals of translational medicine · 2023Article
- Review
- COVID-19-Associated Encephalopathy-Case Series and Clinical Considerations.Journal of clinical medicine · 2022Article
- Whole patient knowledge modeling of COVID-19 symptomatology reveals common molecular mechanisms.Frontiers in molecular medicine · 2022Article
- ADAM17 knockdown mitigates while ADAM17 overexpression aggravates cardiac fibrosis and dysfunctionFrontiers in pharmacology · 2022Article
- Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart.Frontiers in physiology · 2022Article
- Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point.Cells · 2021Review
- Targeting ACE2 for COVID-19 Therapy: Opportunities and Challenges.American journal of respiratory cell and molecular biology · 2021Review
- Angiotensin-Converting-Enzyme 2 and Renin-Angiotensin System Inhibitors in COVID-19: An Update.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2021Review
- An update on ACE2 amplification and its therapeutic potential.Acta physiologica (Oxford, England) · 2021Review
- Angiotensin-(1-7) Expressed From Lactobacillus Bacteria Protect Diabetic Retina in Mice.Translational vision science & technology · 2020Article
- Brain angiotensin converting enzyme-2 in central cardiovascular regulation.Clinical science (London, England : 1979) · 2020Review
- Renin-Angiotensin System overactivation in polycystic ovary syndrome, a risk for SARS-CoV-2 infection?Metabolism open · 2020Article
- Angiotensin-(1-7): Translational Avenues in Cardiovascular Control.American journal of hypertension · 2019Review
- AMPK: a balancer of the renin-angiotensin system.Bioscience reports · 2019Review
- Sex differences in the metabolic effects of the renin-angiotensin system.Biology of sex differences · 2019Review
- The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7).Physiological reviews · 2018Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
We evaluated the hypothesis that activation of endogenous angiotensin-converting enzyme (ACE) 2 would improve cardiac dysfunction induced by diabetes. Ten days after diabetes induction (streptozotocin, 50 mg/kg, i.v.), male Wistar rats were treated with the ACE2 activator 1-[[2-(dimethylamino)ethyl]amino]-4-(hydroxymethyl)-7-[[(4-methylphenyl)sulfonyl]oxy]-9H-xanthen-9-one (XNT, 1 mg/kg/day, gavage) or saline (control) for 30 days. Echocardiography was performed to analyze the cardiac function and kinetic fluorogenic assays were used to determine cardiac ACE and ACE2 activities. Cardiac ACE2, ACE, Mas receptor, AT(1) receptor, AT(2) receptor and collagen types I and III mRNA and ACE2, ACE, Mas, AT(1) receptor, AT(2) receptor, ERK1/2, Akt, AMPK-α and AMPK-β(1) protein were measured by qRT-PCR and western blotting techniques, respectively. Histological sections of hearts were analyzed to evaluate the presence of hypertrophy and fibrosis. Diabetic animals presented hyperglycemia and diastolic dysfunction along with cardiac hypertrophy and fibrosis. XNT treatment prevented further increase in glycemia and improved the cardiac function, as well as the hypertrophy and fibrosis. These effects were associated with increases in cardiac ACE2/ACE ratios (activity: ~26%; mRNA: ~113%; and protein: ~188%) and with a decrease in AT(1) receptor expression. Additionally, XNT inhibited ERK1/2 phosphorylation and prevented changes in AMPK-α and AMPK-β(1) expressions. XNT treatment did not induce any significant change in AT(2) receptor and Akt expression. These results indicate that activation of intrinsic cardiac ACE2 by oral XNT treatment protects the heart against diabetes-induced dysfunction through mechanisms involving ACE, ACE2, ERK1/2, AMPK-α and AMPK-β(1) modulations.
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Registered trials
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