ArticleThe Journal of clinical investigation2014
Cardiac myocyte-secreted cAMP exerts paracrine action via adenosine receptor activation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 82 citations in OpenAlex.
- Extracellular-cAMP suppresses pulmonary arterial hypertension-induced ventricular arrhythmias.Journal of molecular and cellular cardiology · 2026Article
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- Sympathovagal crosstalk: Y2-receptor blockade enhances vagal effects which in turn reduce NPY levels via muscarinic receptor activation.Cardiovascular research · 2025Article
- Identification and Verification of Potential Markers Related to Myocardial Fibrosis by Bioinformatics Analysis.Biochemical genetics · 2025Review
- Structural basis of human ABCC4 recognition of cAMP and ligand recognition flexibility.Cell & bioscience · 2025Article
- The Purinergic Nature of Pseudoxanthoma Elasticum.Biology · 2024Review
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Mitochondrial dysfunction is a key link involved in the pathogenesis of sick sinus syndrome: a review.Frontiers in cardiovascular medicine · 2024Review
- The effect of extracorporeal shock wave on joint capsule fibrosis based on AJournal of orthopaedic surgery and research · 2023Article
- Role of cAMP in Cardiomyocyte Viability: Beneficial or Detrimental?Circulation research · 2023Article
- Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice.Nature communications · 2023Article
- Pharmacological Modulation by Low Molecular Weight Heparin of Purinergic Signaling in Cardiac Cells Prevents Arrhythmia and Lethality Induced by Myocardial Infarction.Journal of cardiovascular development and disease · 2023Article
- Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation.Biomedicines · 2022Review
- Epi-MEIF: detecting higher order epistatic interactions for complex traits using mixed effect conditional inference forests.Nucleic acids research · 2022Article
- MicroRNAs as therapeutic targets in cardiovascular disease.The Journal of clinical investigation · 2022Review
- EnterotoxigenicInfection and immunity · 2022Article
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- Fibroblast-specific activation of Rnd3 protects against cardiac remodeling in diabetic cardiomyopathy via suppression of Notch and TGF-β signaling.Theranostics · 2022Article
- Osteocrin, a novel myokine, prevents diabetic cardiomyopathy via restoring proteasomal activity.Cell death & disease · 2021Article
- Cardiac fibrosis.Cardiovascular research · 2021Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute stimulation of cardiac β-adrenoceptors is crucial to increasing cardiac function under stress; however, sustained β-adrenergic stimulation has been implicated in pathological myocardial remodeling and heart failure. Here, we have demonstrated that export of cAMP from cardiac myocytes is an intrinsic cardioprotective mechanism in response to cardiac stress. We report that infusion of cAMP into mice averted myocardial hypertrophy and fibrosis in a disease model of cardiac pressure overload. The protective effect of exogenous cAMP required adenosine receptor signaling. This observation led to the identification of a potent paracrine mechanism that is dependent on secreted cAMP. Specifically, FRET-based imaging of cAMP formation in primary cells and in myocardial tissue from murine hearts revealed that cardiomyocytes depend on the transporter ABCC4 to export cAMP as an extracellular signal. Extracellular cAMP, through its metabolite adenosine, reduced cardiomyocyte cAMP formation and hypertrophy by activating A1 adenosine receptors while delivering an antifibrotic signal to cardiac fibroblasts by A2 adenosine receptor activation. Together, our data reveal a paracrine role for secreted cAMP in intercellular signaling in the myocardium, and we postulate that secreted cAMP may also constitute an important signal in other tissues.
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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.