The CXCL12γ/ACKR3 Axis Is a Critical Determinant of Myocardial Angiogenesis and Functional Recovery After Infarction
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.
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BibTeX
@article{duval2026cxcl12γackr3,
title = {{The CXCL12γ/ACKR3 Axis Is a Critical Determinant of Myocardial Angiogenesis and Functional Recovery After Infarction}},
author = {Vincent Duval and Morgane Aubert and Alina Ramazanova and Paul Alayrac and Ecem Sakalli and Clément Cochain and Feriel Hamidou and Alexandra Achab Ali and Jose Vilar and Mathilde Lemitre and Stéphane Camus and Bernard Masri and Ralf Jockers and Julie Dam and Thierry Durroux and Jean-Sébastien Silvestre and Angélique Levoye},
journal = {JACC : Basic to Translational Science},
year = {2026},
month = aug,
doi = {10.1016/j.jacbts.2026.101652},
url = {https://hal.science/hal-05775701v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The CXCL12γ/ACKR3 Axis Is a Critical Determinant of Myocardial Angiogenesis and Functional Recovery After Infarction
AU - Vincent Duval
AU - Morgane Aubert
AU - Alina Ramazanova
AU - Paul Alayrac
AU - Ecem Sakalli
AU - Clément Cochain
AU - Feriel Hamidou
AU - Alexandra Achab Ali
AU - Jose Vilar
AU - Mathilde Lemitre
AU - Stéphane Camus
AU - Bernard Masri
AU - Ralf Jockers
AU - Julie Dam
AU - Thierry Durroux
AU - Jean-Sébastien Silvestre
AU - Angélique Levoye
PY - 2026
DA - 2026/08/24
JO - JACC : Basic to Translational Science
DO - 10.1016/j.jacbts.2026.101652
UR - https://hal.science/hal-05775701v1
AB - 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.
SN - 2452-302X
ER -