ArticleHypertension (Dallas, Tex. : 1979)2014
Angiotensin II mediates angiotensin converting enzyme type 2 internalization and degradation through an angiotensin II type I receptor-dependent mechanism.
Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 187 papers, 5 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
187 citing papers in PubMed, 5 syntheses or guidelines pooled it, 279 citations in OpenAlex.
- COVID-19 in comorbid chronic diseased patients, pregnant and lactating women: pathophysiology, available drug treatment, and the most suitable protocol regimen in each group.Inflammopharmacology · 2025Pooled it
- Pooled it
- Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2020Pooled it
- Severe acute respiratory syndrome coronavirus 2 and renin-angiotensin system blockers: A review and pooled analysis.Archives of cardiovascular diseases · 2020Pooled it
- Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults: A Living Systematic Review.Annals of internal medicine · 2020Pooled it
- Severe Acute Hypertension Causes Hemolysis With Release of PEP and ACE Inhibitor.Hypertension (Dallas, Tex. : 1979) · 2026Article
- METTL3 mediates mJournal of advanced research · 2026Article
- Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
- RAAS antagonists dampen the SARS-CoV-2 infection in ex-vivo cultured human precision-cut lung slices.Respiratory research · 2026Article
- Roles of Reactive Oxygen Species in Relationships Between Viral Infections and Alzheimer's Disease and Related Dementia.Antioxidants (Basel, Switzerland) · 2026Review
- Porcine hemagglutinating encephalomyelitis virus VW572 (not Gent/PS412 and Labadie) uses the CD81 receptor and MVB-derived exosomal pathway for efficient entry and spread in neuronal cells.Journal of virology · 2025Article
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- Analysis of modifying factors for ACE2 to work effectively.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- COVID-19 and acute limb ischemia: latest hypotheses of pathophysiology and molecular mechanisms.Journal of Zhejiang University. Science. B · 2025Review
- UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Guideline-directed medical therapy prescribing patterns and in-hospital outcomes among heart failure patients during COVID-19.American heart journal plus : cardiology research and practice · 2024Article
- Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19.World journal of gastroenterology · 2024Article
- Activation of limbal epithelial proliferation is partly controlled by the ACE2-LCN2 pathway.iScience · 2024Article
- Article
- Cardiovascular Comorbidities in COVID-19: Comprehensive Analysis of Key Topics.Interactive journal of medical research · 2024Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issuedSriramula, Srinivas [added]
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Angiotensin-converting enzyme type 2 (ACE2) is a pivotal component of the renin-angiotensin system, promoting the conversion of angiotensin II (Ang-II) to Ang-(1-7). We previously reported that decreased ACE2 expression and activity contributes to the development of Ang-II-mediated hypertension in mice. The present study aimed to investigate the mechanisms involved in ACE2 downregulation during neurogenic hypertension. In ACE2-transfected Neuro-2A cells, Ang-II treatment resulted in a significant attenuation of ACE2 enzymatic activity. Examination of the subcellular localization of ACE2 revealed that Ang-II treatment leads to ACE2 internalization and degradation into lysosomes. These effects were prevented by both the Ang-II type 1 receptor (AT1R) blocker losartan and the lysosomal inhibitor leupeptin. In contrast, in HEK293T cells, which lack endogenous AT1R, Ang-II failed to promote ACE2 internalization. Moreover, this effect could be induced after AT1R transfection. Furthermore, coimmunoprecipitation experiments demonstrated that AT1R and ACE2 form complexes, and these interactions were decreased by Ang-II treatment, which also enhanced ACE2 ubiquitination. In contrast, ACE2 activity was not changed by transfection of AT2 or Mas receptors. In vivo, Ang-II-mediated hypertension was blunted by chronic infusion of leupeptin in wildtype C57Bl/6, but not in ACE2 knockout mice. Overall, this is the first demonstration that elevated Ang-II levels reduce ACE2 expression and activity by stimulation of lysosomal degradation through an AT1R-dependent mechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.