ArticleNature2012
APJ acts as a dual receptor in cardiac hypertrophy.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03084679 (Characterization of Myocardial Interstitial Fibrosis and Cardiomyocyte Hypertrophy by Cardiac MRI In Heart Failure), which is not on this map. Cited by 116 papers.
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.
Characterization of Myocardial Interstitial Fibrosis and Cardiomyocyte Hypertrophy by Cardiac MRI In Heart Failure: Implication on Early Remodeling and on the Transition to Heart Failure
Who cites it
116 citing papers in PubMed, 235 citations in OpenAlex.
- 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
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- Targeting the Apelin-APJ Axis: A Promising Strategy to Mitigate Anthracycline-Induced Cardiotoxicity.Cardiovascular toxicology · 2026Review
- Therapeutic Strategies Targeting the Kidney-Liver-Immune-Heart Network: Circadian and Mechanosensory Pathways in CKD-Associated Cardiac Injury.International journal of molecular sciences · 2026Review
- Dynamic monomer-dimer transition in ligand-induced apelin receptor activation.Nature communications · 2026Article
- 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
- Signaling pathway alterations in hearts of a porcine model harboring a β-myosin heavy chain (MYH7-R403Q) gene variant.Journal of molecular and cellular cardiology plus · 2025Article
- The Impact of the Apelinergic System on the Cardiovascular System.International journal of molecular sciences · 2025Review
- Mechanistic insights into the versatile stoichiometry and biased signaling of the apelin receptor-arrestin complex.Nature communications · 2025Article
- In vivo measurement of an Apelin gradient with a genetically encoded APLNR conformation biosensor.Nature communications · 2025Article
- A force-sensitive adhesion GPCR is required for equilibrioception.Cell research · 2025Article
- Harnessing the power of structure-based design: A new lease on life for cardiovascular drug development with apelin receptor modulators.Clinical and translational medicine · 2024Article
- The significance of the apelinergic system in doxorubicin-induced cardiotoxicity.Heart failure reviews · 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
- Targeting the apelin system for the treatment of cardiovascular diseases.Cardiovascular research · 2023Review
- APJ as Promising Therapeutic Target of Peptide Analogues in Myocardial Infarction- and Hypertension-Induced Heart Failure.Pharmaceutics · 2023Review
- Current Strategies for Engineered Vascular Grafts and Vascularized Tissue Engineering.Polymers · 2023Review
- Chronic Effects of Apelin on Cardiovascular Regulation and Angiotensin II-Induced Hypertension.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Structure-function relationship and physiological role of apelin and its G protein coupled receptor.Biophysical reviews · 2023Review
56 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
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues. Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate Gαi and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of β-arrestins or by pharmacological doses of apelin acting through Gαi. Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy.
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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.