title: Distinct effects of inflammation on preconditioning and regeneration of the adult zebrafish heart.
abstract: The adult heart is able to activate cardioprotective programmes and modifies its architecture in response to physiological or pathological changes. While mammalian cardiac remodelling often involves hypertrophic expansion, the adult zebrafish heart exploits hyperplastic growth. This capacity depends on the responsiveness of zebrafish cardiomyocytes to mitogenic signals throughout their entire life. Here, we have examined the role of inflammation on the stimulation of cell cycle activity in the context of heart preconditioning and regeneration. We used thoracotomy as a cardiac preconditioning model and cryoinjury as a model of cardiac infarction in the adult zebrafish. First, we performed a spatio-temporal characterization of leucocytes and cycling cardiac cells after thoracotomy. This analysis revealed a concomitance between the infiltration of inflammatory cells and the stimulation of the mitotic activity. However, decreasing the immune response using clodronate liposome injection, PLX3397 treatment or anti-inflammatory drugs surprisingly had no effect on the re-entry of cardiac cells into the cell cycle. In contrast, reducing inflammation using the same strategies after cryoinjury strongly impaired cardiac cell mitotic activity and the regenerative process. Taken together, our results show that, while the immune response is not necessary to induce cell-cycle activity in intact preconditioned hearts, inflammation is required for the regeneration of injured hearts in zebrafish.
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: de Preux Charles
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bise
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Baier
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Marro
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland anna.jazwinska@unifr.ch.
authors.forename: Anna
authors.initials: A
authors.lastname: Jaźwińska
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002453:Cell Cycle; D049109:Cell Proliferation; D015925:Cryopreservation; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007962:Leukocytes / Q000166:cytology; D009203:Myocardial Infarction / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000276:immunology; D011758:Pyrroles / Q000494:pharmacology; D012038:Regeneration; D013908:Thoracotomy; D015027:Zebrafish / Q000502:physiology
chemical_list: D000631:Aminopyridines; D000893:Anti-Inflammatory Agents; D011758:Pyrroles; C000600259:pexidartinib
keywords: cardiac muscle; cardiomyocyte; cryoinjury; leucocytes; non-mammalian animal model; thoracotomy