Pro-Angiogenic Macrophage Phenotype to Promote Myocardial Repair
2019 | journal article. A publication with affiliation to the University of Göttingen.
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Pro-Angiogenic Macrophage Phenotype to Promote Myocardial Repair
Ferraro, B.; Leoni, G.; Hinkel, R.; Ormanns, S.; Paulin, N.; Ortega-Gomez, A. & Viola, J. R. et al. (2019)
Journal of the American College of Cardiology, 73(23) pp. 2990-3002. DOI: https://doi.org/10.1016/j.jacc.2019.03.503
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Details
- Authors
- Ferraro, Bartolo; Leoni, Giovanna; Hinkel, Rabea; Ormanns, Steffen; Paulin, Nicole; Ortega-Gomez, Almudena; Viola, Joana R.; de Jong, Renske; Bongiovanni, Dario; Bozoglu, Tarik; Maas, Sanne L.; D’Amico, Michele; Kessler, Thorsten; Zeller, Tanja; Hristov, Michael; Reutelingsperger, Chris; Sager, Hendrik B.; Döring, Yvonne; Nahrendorf, Matthias; Kupatt, Christian; Soehnlein, Oliver
- Abstract
- BACKGROUND: Heart failure following myocardial infarction (MI) remains one of the major causes of death worldwide, and its treatment is a crucial challenge of cardiovascular medicine. An attractive therapeutic strategy is to stimulate endogenous mechanisms of myocardial regeneration. OBJECTIVES: This study evaluates the potential therapeutic treatment with annexin A1 (AnxA1) to induce cardiac repair after MI. METHODS: AnxA1 knockout (AnxA1-/-) and wild-type mice underwent MI induced by ligation of the left anterior descending coronary artery. Cardiac functionality was assessed by longitudinal echocardiographic measurements. Histological, fluorescence-activated cell sorting, dot blot analysis, and in vitro/ex vivo studies were used to assess the myocardial neovascularization, macrophage content, and activity in response to AnxA1. RESULTS: AnxA1-/- mice showed a reduced cardiac functionality and an expansion of proinflammatory macrophages in the ischemic area. Cardiac macrophages from AnxA1-/- mice exhibited a dramatically reduced ability to release the proangiogenic mediator vascular endothelial growth factor (VEGF)-A. However, AnxA1 treatment enhanced VEGF-A release from cardiac macrophages, and its delivery in vivo markedly improved cardiac performance. The positive effect of AnxA1 treatment on cardiac performance was abolished in wild-type mice transplanted with bone marrow derived from Cx3cr1creERT2Vegfflox/flox or in mice depleted of macrophages. Similarly, cardioprotective effects of AnxA1 were obtained in pigs in which full-length AnxA1 was overexpressed by use of a cardiotropic adeno-associated virus. CONCLUSIONS: AnxA1 has a direct action on cardiac macrophage polarization toward a pro-angiogenic, reparative phenotype. AnxA1 stimulated cardiac macrophages to release high amounts of VEGF-A, thus inducing neovascularization and cardiac repair.
- Issue Date
- 2019
- Journal
- Journal of the American College of Cardiology
- Language
- English