Evidence map›Paper›PMID 41875505›Full record

ReviewPharmacological reviews2026

G protein-coupled receptors and inflammation resolution signaling networks in the heart: Pharmacology and potential for innovative therapeutics.

Deanna K Sosnowski, Terence E Hébert, Dobromir Dobrev, Stanley Nattel

Abstract readReview
In one paragraph

Review in Pharmacological reviews, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Deanna K SosnowskiDepartment of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada; Montreal Heart Institute Research Centre, Université de Montréal, Montréal, Québec, Canada.
Terence E HébertDepartment of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
Dobromir DobrevMontreal Heart Institute Research Centre, Université de Montréal, Montréal, Québec, Canada; Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany; Department of Integrative Physiology, Baylor College of Medicine, Houston, Texas.
Stanley NattelDepartment of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada; Montreal Heart Institute Research Centre, Université de Montréal, Montréal, Québec, Canada; Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany; Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada. Electronic address: stanley.nattel@icm-mhi.org.

Funding

The Role of Inflammasome in the Pathogenesis of Atrial FibrillationR01HL136389 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Na Li · 2017 to 2026
$5.6M
Resolution of inflammation and atrial fibrillationR01HL165704 · NHLBI · UNIVERSITY OF MINNESOTA · PI SAMUEL C DUDLEY · 2023 to 2026
$2.9M
Cardiac fibroblast inflammasome and atrial myopathyR01HL163277 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI LI, NA · 2022 to 2025
$2.8M
Role of Nucleoside-Diphosphate Kinase Signaling in Atrial FibrillationR01HL160992 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Xander H.T. Wehrens · 2023 to 2026
$2.1M
FKBP5 AND CARDIAC ARRHYTHMOGENESISR01HL164838 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Na Li · 2024 to 2026
$1.7M
Calcium Driven Fibroblast Dysregulation in Human Atrial Profibrotic RemodelingR01HL176651 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Eleonora Grandi · 2025 to 2026
$1.1M
NHLBI NIH HHS R01 HL160992NHLBI NIH HHS R01 HL163277NHLBI NIH HHS R01 HL164838NHLBI NIH HHS R01 HL165704NHLBI NIH HHS R01 HL176651NIH R01HL136389
6 · The paper itself

Abstract

Chronic, unresolved inflammation, and immune system activation contribute to the development and progression of human cardiovascular disease. Specialized proresolving mediators (SPMs), primarily the lipoxins and resolvins, demonstrate potent inflammation-resolving effects. SPMs bind to their respective G protein-coupled receptors (GPCRs) to transduce intracellular events and exert proresolving actions. Given the importance of immune cells in the cardiovascular system, the involvement of nonimmune cardiac cell-types in chronic cardiac inflammation, and the inflammation-resolving effects of SPMs, SPM-GPCR interactions may present efficacious new therapeutic targets for heart disease. In this review, we discuss the mechanisms potentially underlying these GPCR-mediated responses. We begin by providing a brief overview of SPM biosynthesis and the GPCRs implicated in SPM signaling. We then discuss literature demonstrating protective effects of SPMs in models of heart disease. We look in detail at the pharmacology of SPM-GPCR interactions, with a primary focus on formyl peptide receptor 2, GPR32, GPR18, and chemerin receptor 1. We then consider SPM-GPCR downstream signaling pathways in various cell models, including heterologous cell systems overexpressing human SPM-GPCR constructs, SPM-GPCR interactions in endogenous immune cells and effects in nonimmune cell types of the heart including cardiomyocytes, cardiac fibroblasts, endothelial cells, and vascular smooth muscle cells. We end by considering knowledge gaps and discussing future directions in SPM-GPCR interaction research. SPM-GPCR signaling networks and actions vary widely in different cell-types and disease contexts, and knowledge of the detailed pharmacology in the heart is quite limited, so extensive additional work on SPM-GPCR signaling is needed to capitalize on the rich therapeutic potential. SIGNIFICANCE STATEMENT: Inflammation resolution is a critical process in cardiac healing after injury or disease. Understanding of the pharmacology and G protein-coupled receptor-dependent signaling mechanisms of inflammation-resolving molecules in the heart is limited, heavily dependent on cell type, and sometimes conflicting. The knowledge gained about these signaling mechanisms in more basic cell systems can be used to facilitate future investigation of how these molecules work within the diverse cardiac cellular milieu as potential targeted therapeutics for heart disease.

Indexed as

Heart DiseasesInflammationMyocardiumReceptors, G-Protein-CoupledAnimalsHumansSignal TransductionSpecialized Pro-Resolving MediatorsReceptors, G-Protein-Coupled

Identifiers

PMID41875505
PMCPMC13197962

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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.