Author + information
- Received February 21, 2019
- Revision received May 29, 2019
- Accepted June 4, 2019
- Published online October 28, 2019.
- Mathilde Prud’homme, PhDa,
- Maxime Coutrot, MD, MSca,b,∗,
- Thibault Michel, MD, MSca,∗,
- Louis Boutin, MD, MSca,b,∗,
- Magali Genest, PhDa,d,
- Françoise Poirier, PhDc,
- Jean-Marie Launay, PharmD, PhDa,
- Bocar Kanef,
- Satoshi Kinugasa, MD, PhDd,
- Niki Prakoura, PhDd,
- Sophie Vandermeerschd,
- Alain Cohen-Solal, MD, PhDa,e,
- Claude Delcayre, PhDa,
- Jane-Lise Samuel, MD, PhDa,
- Ravindra Mehta, MDg,
- Etienne Gayat, MD, PhDa,b,
- Alexandre Mebazaa, MD, PhDa,b,
- Christos E. Chadjichristos, PhDd,† and
- Matthieu Legrand, MD, PhDa,b,h,†∗ ()
- aINSERM UMR-S 942, Institut National de la Santé et de la Recherche Médicale (INSERM), Lariboisière Hospital, and INI-CRCT-F-CRIN, Paris, France
- bAP-HP, St-Louis-Lariboisière Hospital, Department of Anesthesiology and Critical Care and Burn Unit, University Paris Diderot, Paris, France
- cInstitut Jacques Monod, Team: Morphogenesis, Homeostasis and Pathologies, Paris, France
- dINSERM UMR-S 1155, Tenon Hospital, Paris, France
- eCardiology Department, Lariboisière Hospital, Paris, France
- fUMS-28 Phénotypage du petit animal, Université Pierre et Marie Curie, Paris, France
- gDepartment of Medicine, University of California-San Diego, San Diego, California
- hDepartment of Anesthesiology and peri-operative Care, University of California San Francisco, United States
- ↵∗Address for correspondence:
Dr. Matthieu M. Legrand, Department of Anesthesiology and Peri-Operative Care, University of California San Francisco, 500 Parnassus Avenue, E410, San Francisco, California 94117.
• In 2 different mouse models, AKI increased Gal-3 expression and induced cardiac dysfunction, cardiac and systemic inflammation, cardiac macrophage infiltration, and fibrosis.
• Cardiac consequences of AKI were dependent on the Gal-3 pathway and were prevented using Gal-3 knockout mice or modified citrus pectin as a pharmaceutical inhibitor.
• Cardiac Gal-3 expression resulted from bone marrow-derived immune cells recruitment after AKI.
• In critically ill patients, development of AKI is associated with increased plasma Gal-3 levels and increased biomarkers of cardiac injury and damage.
Acute kidney injury is associated with increased risk of heart failure and mortality. This study demonstrates that acute kidney injury induces remote cardiac dysfunction, damage, injury, and fibrosis via a galectin-3 (Gal-3) dependent pathway. Gal-3 originates from bone marrow-derived immune cells. Cardiac damage could be prevented by blocking this pathway.
↵∗ Drs. Coutrot, Michel, and Boutin contributed equally to this work and are joint first authors.
↵† Drs. Chadjichristos and Legrand contributed equally to this work and are joint senior authors.
This work was supported by “Institut National de la Santé et de la Recherche Médicale (INSERM)” and by Paris Diderot University and the Société Française d’Anesthésie et de Réanimation (SFAR). Dr. Prud’homme was supported by a Ph.D. training grant from Paris Diderot University and “Groupe de Réflexion sur la Recherche Cardiovasculaire (GRRC).” Dr. Cohen-Solal has received grants and fees from Novartis, Servier, Vifor, AstraZeneca, and Merck & Co. Inc. Dr. Mehta has been a consultant, a member of the advisory board for Baxter, AM Pharma, CSL-Behring, Astute Medical Inc. Regulus, Akebia, Intercept, Mallinckrodt, and Ferring; and has received grants from Relypsa, Fresenius-Kabi; Fresenius, and Grifols. Dr. Gayat has been a consultant for Magnisense and Adrenomed; and has received research grants from Deltex Medical and Retia Medical. Dr. Legrand has received research support from Sphingotec; has received lecture fees from Baxter and Fresenius; and has received consultancy fees from Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received February 21, 2019.
- Revision received May 29, 2019.
- Accepted June 4, 2019.
- 2019 The Authors