Pro-Angiogenic Macrophage Phenotype to Promote Myocardial Repair
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Pro-Angiogenic Macrophage Phenotype to Promote Myocardial Repair. / 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.
in: J AM COLL CARDIOL, Jahrgang 73, Nr. 23, 18.06.2019, S. 2990-3002.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Pro-Angiogenic Macrophage Phenotype to Promote Myocardial Repair
AU - Ferraro, Bartolo
AU - Leoni, Giovanna
AU - Hinkel, Rabea
AU - Ormanns, Steffen
AU - Paulin, Nicole
AU - Ortega-Gomez, Almudena
AU - Viola, Joana R
AU - de Jong, Renske
AU - Bongiovanni, Dario
AU - Bozoglu, Tarik
AU - Maas, Sanne L
AU - D'Amico, Michele
AU - Kessler, Thorsten
AU - Zeller, Tanja
AU - Hristov, Michael
AU - Reutelingsperger, Chris
AU - Sager, Hendrik B
AU - Döring, Yvonne
AU - Nahrendorf, Matthias
AU - Kupatt, Christian
AU - Soehnlein, Oliver
N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2019/6/18
Y1 - 2019/6/18
N2 - 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.
AB - 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.
KW - Animals
KW - Annexin A1/deficiency
KW - Female
KW - Macrophages/physiology
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Myocardial Infarction/genetics
KW - Myocardium/metabolism
KW - Neovascularization, Physiologic/physiology
KW - Phenotype
U2 - 10.1016/j.jacc.2019.03.503
DO - 10.1016/j.jacc.2019.03.503
M3 - SCORING: Journal article
C2 - 31196457
VL - 73
SP - 2990
EP - 3002
JO - J AM COLL CARDIOL
JF - J AM COLL CARDIOL
SN - 0735-1097
IS - 23
ER -