Evidence map›Paper›PMID 37737772›Full record

ArticleJACC. Clinical electrophysiology2023

Enhanced Myocardial Adenylyl Cyclase Activity Alters Heart-Brain Communication.

Jacopo Agrimi, Danilo Menicucci, Jia-Hua Qu, Marco Laurino, Chelsea D Mackey, Laila Hasnain, Yelena S Tarasova, Kirill V Tarasov, Ross A McDevitt, Donald B Hoover and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. Clinical electrophysiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Metabolism-Mediated Regulation of Brain-Heart Interactions.International journal of molecular sciences · 2026
    Review
  4. Heart-Brain Axis: Subclinical Cardiovascular Changes and Brain Health.Journal of the American Heart Association · 2026
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Jacopo AgrimiDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health Biomedical Research Center (BRC), Baltimore, Maryland, USA; Department of Biomedical Sciences, University of Padova, Padova, Italy.
Danilo MenicucciDepartment of Surgical, Medical, Molecular Pathology, and Critical Care Medicine, University of Pisa, Pisa, Italy.
Jia-Hua QuLaboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health Biomedical Research Center (BRC), Baltimore, Maryland, USA.
Marco LaurinoInstitute of Clinical Physiology, National Research Council, Pisa, Italy.
Chelsea D MackeyLaboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health Biomedical Research Center (BRC), Baltimore, Maryland, USA.
Laila HasnainLaboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health Biomedical Research Center (BRC), Baltimore, Maryland, USA.
Yelena S TarasovaLaboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health Biomedical Research Center (BRC), Baltimore, Maryland, USA.
Kirill V TarasovLaboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health Biomedical Research Center (BRC), Baltimore, Maryland, USA.
Ross A McDevittCenter of Excellence in Inflammation, Infectious Disease, and Immunity, East Tennessee State University, Johnson City, Tennessee, USA.
Donald B HooverThe Comparative Medicine Section, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA; Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA; Center of Excellence in Inflammation, Infectious Disease, and Immunity, East Tennessee State University, Johnson City, Tennessee, USA.
Angelo GemignaniDepartment of Surgical, Medical, Molecular Pathology, and Critical Care Medicine, University of Pisa, Pisa, Italy.
Nazareno PaolocciDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Biomedical Sciences, University of Padova, Padova, Italy. Electronic address: npaoloc1@jhmi.edu.
Edward G LakattaLaboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health Biomedical Research Center (BRC), Baltimore, Maryland, USA. Electronic address: lakattae@grc.nia.nih.gov.
National Institutes of Health · USEast Tennessee State University · USUniversity of Pisa · ITIstituto di Fisiologia Clinica · ITUniversity of Padua · IT

Funding

BDNF TrkB- and beta-AR signals in ischemic and non-ischemic cardiomyopathyR01HL136918 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI PAOLOCCI, NAZARENO · 2018 to 2021
$2.7M
Intramural NIH HHS Z99 AG999999NHLBI NIH HHS R01 HL136918
6 · The paper itself

Abstract

backgroundThe central nervous system's influence on cardiac function is well described; however, direct evidence for signaling from heart to brain remains sparse. Mice with cardiac-selective overexpression of adenylyl cyclase type 8 (TGAC8) display elevated heart rate/contractility and altered neuroautonomic surveillance.

objectivesIn this study the authors tested whether elevated adenylyl cyclase type 8-dependent signaling at the cardiac cell level affects brain activity and behavior.

methodsA telemetry system was used to record electrocardiogram (ECG) and electroencephalogram (EEG) in TGAC8 and wild-type mice simultaneously. The Granger causality statistical approach evaluated variations in the ECG/EEG relationship. Mouse behavior was assessed via elevated plus maze, open field, light-dark box, and fear conditioning tests. Transcriptomic and proteomic analyses were performed on brain tissue lysates.

resultsBehavioral testing revealed increased locomotor activity in TGAC8 that included a greater total distance traveled (+43%; P < 0.01), a higher average speed (+38%; P < 0.01), and a reduced freezing time (-45%; P < 0.01). Dual-lead telemetry recording confirmed a persistent heart rate elevation with a corresponding reduction in ECG-R-waves interval variability and revealed increased EEG-gamma activity in TGAC8 vs wild-type. Bioinformatic assessment of hippocampal tissue indicated upregulation of dopamine 5, gamma-aminobutyric acid A, and metabotropic glutamate 1/5 receptors, major players in gamma activity generation. Granger causality analyses of ECG and EEG recordings showed a marked increase in informational flow between the TGAC8 heart and brain.

conclusionsPerturbed signals arising from the heart cause changes in brain activity, altering mouse behavior. More specifically, the brain interprets augmented myocardial humoral/functional output as a "sustained exercise-like" situation and responds by activating central nervous system output controlling locomotion.

Indexed as

Adenylyl CyclasesBehaviorHeartProteomicsAnimalsBrainMiceadenylyl cyclase 8Adenylyl Cyclasesadenylyl cyclase type 8electroencephalogram gamma rhythmGranger causalityheart-brain communicationlocomotor activitystress

Identifiers

PMID37737772
PMCPMC12312800
OpenAlexW4386885207

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.