ArticleOncotarget2017
Angiotensin-converting enzyme 2 overexpression protects against doxorubicin-induced cardiomyopathy by multiple mechanisms in rats.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Overexpression of angiotensin-converting enzyme 2 by renin-angiotensin system inhibitors. Truth or myth? A systematic review of animal studies.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Pooled it
- Unraveling the interplay between RAS axes and NOX signaling in fibroblasts during cardiac fibrosis.Molecular and cellular biochemistry · 2026Review
- Chemotherapy-induced cardiotoxicity in breast cancer: mechanisms, diagnostic advances, and emerging protective strategies.American journal of physiology. Heart and circulatory physiology · 2025Review
- NADPH Oxidases in Cancer Therapy-Induced Cardiotoxicity: Mechanisms and Therapeutic Approaches.Cardiovascular toxicology · 2025Review
- 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
- Metformin Alleviates Epirubicin-Induced Endothelial Impairment by Restoring Mitochondrial Homeostasis.International journal of molecular sciences · 2022Article
- Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: a potential prognostic marker for breast cancer patients receiving chemotherapy.Journal of translational medicine · 2022Article
- Anthracycline-induced cardiotoxicity and renin-angiotensin-aldosterone system-from molecular mechanisms to therapeutic applications.Heart failure reviews · 2022Review
- Alternative RAS in Various Hypoxic Conditions: From Myocardial Infarction to COVID-19.International journal of molecular sciences · 2021Review
- BMP-2 alleviates heart failure with type 2 diabetes mellitus and doxorubicin-induced AC16 cell injury by inhibiting NLRP3 inflammasome-mediated pyroptosis.Experimental and therapeutic medicine · 2021Article
- A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor.Pharmacology & therapeutics · 2021Review
- Article
- P21‑activated kinase 1 mediates angiotensin II‑induced differentiation of human atrial fibroblasts via the JNK/c‑Jun pathway.Molecular medicine reports · 2021Article
- What is considered cardiotoxicity of anthracyclines in animal studies.Oncology reports · 2020Review
- Downregulation of miR-3568 Protects Against Ischemia/Reperfusion-Induced Cardiac Dysfunction in Rats and Apoptosis in H9C2 Cardiomyocytes Through Targeting TRIM62.Frontiers in pharmacology · 2020Article
- [Daxx overexpression inhibits AngⅡ-induced proliferation and migration in vascular smooth muscle cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- AMPK: a balancer of the renin-angiotensin system.Bioscience reports · 2019Review
- Sulforaphane Attenuates Angiotensin II-Induced Vascular Smooth Muscle Cell Migration via Suppression of NOX4/ROS/Nrf2 Signaling.International journal of biological sciences · 2019Article
- AMP-activated Protein Kinase Phosphorylation of Angiotensin-Converting Enzyme 2 in Endothelium Mitigates Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2018Article
- The sirtuin 6 prevents angiotensin II-mediated myocardial fibrosis and injury by targeting AMPK-ACE2 signaling.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiotensin-converting enzyme 2 (ACE2) is considered a potential therapeutic target of the renin-angiotensin system (RAS) for the treatment of cardiovascular diseases. We aimed to explore the effects of ACE2 overexpression on doxorubicin-induced cardiomyopathy in rats. Rats were randomly divided into treatment and control groups. The rats of treatment group were injected intraperitoneally with 6 doses of doxorubicin (2.5 mg/kg) within a period of two weeks. Two weeks after the initial injection of doxorubicin, these rats were randomly divided into Mock, Ad-EGFP, Ad-ACE2, and Cilazapril groups. The rats of Ad-EGFP and Ad-ACE2 groups received intramyocardial injection of Ad-EGFP and Ad-ACE2, respectively. The rats of Cilazapril group received cilazapril (10 mg/kg/day) via intragastric intubation. Apoptosis, inflammation, oxidative stress, cardiac function, the extent of myocardial fibrosis, and levels of ACE2, ACE, angiotensin II (AngII), and angiotensin (1-7) were evaluated. Four weeks after ACE2 gene transfer, the Ad-ACE2 group showed not only reduced apoptosis, inflammatory response, oxidative stress, left ventricular (LV) volume, extent of myocardial fibrosis and mortality of rats, but also increased LV ejection fraction and ACE2 expression level compared with the Mock and Ad-EGFP groups. ACE2 overexpression was superior to cilazapril in improving doxorubicin-induced cardiomyopathy. The putative mechanisms may involve activation of the AMPK and PI3K-AKT pathways, inhibition of the ERK pathway, decrease of TGF-β1 expression, and interactions of shifting RAS components, such as decreased myocardium AngII levels, increased myocardium Ang (1-7) levels, and reduced ACE expression. Thus, ACE2 may be a novel therapeutic approach to prevent and treat doxorubicin-induced cardiomyopathy.
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