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The CXCL12γ/ACKR3 Axis Is a Critical Determinant of Myocardial Angiogenesis and Functional Recovery After Infarction

Year: 2026
Type: article
Abstract: Following myocardial infarction, the CXCL12γ-heparan sulfate-ACKR3 axis emerges as a critical, localized signaling mechanism for cardiac repair. Unlike the α isoform, CXCL12γ exhibits superior affinity for ACKR3. Although genetic disruption of CXCL12γ-heparan sulfate binding impairs postischemic angiogenesis and function, its overexpression rescues these deficits. Mechanistically, cardiomyocyte-specific ACKR3 is vital for the regulation of cardiac function, whereas fibroblast-specific ACKR3 orchestrates a proangiogenic paracrine program. This study identifies CXCL12γ as a noncanonical ligand that activates fibroblast-mediated microvascular expansion via ACKR3, offering a novel therapeutic target to enhance myocardial recovery and preserve cardiac performance.
DOI: 10.1016/j.jacbts.2026.101652
Authors: Vincent Duval, Morgane Aubert, Alina Ramazanova, Paul Alayrac, Ecem T. Sakalli, Clément Cochain, Feriel Hamidou, Alexandra Achab Ali, Jose Vilar, Mathilde Lemitre, Stéphane M. Camus, Bernard Masri, Ralf Jockers, Julie Dam, Thierry Durroux, Jean-Sébastien Silvestre, Angélique Levoye
Institutions: Inserm, Université Paris Cité, Paris Cardiovascular Research Center, Universitätsklinikum Würzburg, Centre National de la Recherche Scientifique, Institut Cochin, Université de Montpellier, Institut de Génomique Fonctionnelle, Université Sorbonne Paris Nord
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $4,750
OpenAlex ID: W7203837453
FWCI:
Cites: 42
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Related to: 10