ArticleThe Journal of clinical investigation2013
Apelin is a positive regulator of ACE2 in failing hearts.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.
- The association between apelin polymorphisms and hypertension in China: A meta-analysis.Journal of the renin-angiotensin-aldosterone system : JRAASPooled it
- Relationship between Angiotensin Converting Enzyme, Apelin, and New-Onset Atrial Fibrillation after Off-Pump Coronary Artery Bypass Grafting.BioMed research international · 2017Trial
- The Apelin-APJ Axis in Heart Failure: Mechanistic Insights, Clinical Evidence, and Translational Challenges.Cardiovascular drugs and therapy · 2026Review
- Apelin-APLNR pathway across development, inflammation, and vascular remodeling: an endothelial perspective.Experimental & molecular medicine · 2026Review
- Review
- Review
- Beyond Leptin and Adiponectin: The Diverse Roles of Adipokines in the Myocardial Hypertrophic Process and Heart Failure and Their Potential Contribution in Obesity.International journal of molecular sciences · 2025Review
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- Overview of exosomal non-coding RNAs in cardiovascular disease using high throughput sequencing.European journal of pharmacology · 2025Review
- Global siRNA screen identifies human host factors critical for SARS-CoV-2 replication and late stages of infection.PLoS biology · 2025Article
- Impact of Glucose, Inflammation and Phytochemicals onAntioxidants (Basel, Switzerland) · 2025Article
- Analysis of Biomarker Levels in Nasopharyngeal Swabs, Serum, and Saliva Across Different Health Conditions.Life (Basel, Switzerland) · 2025Article
- Early Administration of Apelin Could Prevent Heart Failure Following Myocardial Injury; A Systematic Review and Meta-Analysis.Archives of academic emergency medicine · 2025Review
- Angiotensin-Converting Enzyme 2 Posttranslational Modifications and Implications for Hypertension and SARS-CoV-2: 2023 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Food-Derived Up-Regulators and Activators of Angiotensin Converting Enzyme 2: A Review.Journal of agricultural and food chemistry · 2024Review
- The biased apelin receptor agonist, MM07, reverses Sugen/hypoxia-induced pulmonary arterial hypertension as effectively as the endothelin antagonist macitentan.Frontiers in pharmacology · 2024Article
- Protective effects of limb remote ischemic per-conditioning on the heart injury induced by renal ischemic-reperfusion through the interaction of the apelin with the RAS/iNOS pathway.BioImpacts : BI · 2024Article
- Effects of alamandine on monocrotaline-induced pulmonary hypertension in rats.Iranian journal of basic medical sciences · 2024Article
- ACE2: the node connecting the lung cancer and COVID-19.American journal of cancer research · 2024Review
- The possible mechanism and research progress of ACE2 involved in cardiovascular injury caused by COVID-19: a review.Frontiers in cardiovascular medicine · 2024Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2-angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases.
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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.