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Record W3126990883 · doi:10.1101/2021.01.28.428724

Resident Cardiac Macrophages Mediate Adaptive Myocardial Remodeling

2021· preprint· en· W3126990883 on OpenAlexaff
Nicole R. Wong, Jay Mohan, Benjamin J. Kopecky, Shuchi Guo, Lixia Du, Jamison Leid, Oleksandr Dmytrenko, Hannah Luehmann, Geetika Bajpai, Laura Ewald, Lauren Bell, Nikhil Patel, Inessa Lokshina, Andrea Bredemeyer, Carla J. Weinheimer, Jessica Nigro, Attila Kovács, Sachio Morimoto, Peter O. Bayguinov, Max R. Fisher, James A. J. Fitzpatrick, Slava Epelman, Daniel Kreisel, Rajan Sah, Yongjian Liu, Hongzhen Hu, Kory J. Lavine

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldMedicine
TopicCardiac Fibrosis and Remodeling
Canadian institutionsToronto General HospitalUniversity Health Network
FundersNational Institutes of HealthOffice of Research Infrastructure Programs, National Institutes of HealthCenter for Cellular Imaging, Washington UniversityChildren's Discovery InstituteNIH Office of the DirectorNational Heart, Lung, and Blood InstituteFoundation for Barnes-Jewish Hospital
KeywordsCCR2MacrophageInflammationChemokineCell biologyContractilityHeart failurePopulationMyocyteAngiogenesisChemokine receptorBiologyMedicineImmunologyCancer researchInternal medicineIn vitro

Abstract

fetched live from OpenAlex

Summary Cardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2−) macrophages. Herein, we identify an essential role for CCR2− macrophages in the chronically failing heart. Depletion of CCR2− macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2− macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4) dependent pathway that controlled growth factor expression. These findings establish a role for tissue resident macrophages in adaptive cardiac remodeling and introduce a new mechanism of cardiac macrophage activation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.390
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.237
Teacher spread0.219 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations15
Published2021
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicCardiac Fibrosis and RemodelingFrench-language works237,207