Abstract
Following an insult by both intrinsic and extrinsic pathways, complex cellular, and molecular interactions determine a successful recovery or inadequate repair of damaged tissue. The efficiency of this process is particularly important in the heart, an organ characterized by very limited regenerative and repair capacity in higher adult vertebrates. Cardiac insult is characteristically associated with fibrosis and heart failure, as a result of cardiomyocyte death, myocardial degeneration, and adverse remodeling. Recent evidence implies that resident non-cardiomyocytes, fibroblasts but also macrophages -pillars of the innate immunity- form part of the inflammatory response and decisively affect the repair process following a cardiac insult. Multiple studies in model organisms (mouse, zebrafish) of various developmental stages (adult and neonatal) combined with genetically engineered cell plasticity and differentiation intervention protocols -mainly targeting cardiac fibroblasts or progenitor cells-reveal particular roles of resident and recruited innate immune cells and their secretome in the coordination of cardiac repair. The interplay of innate immune cells with cardiac fibroblasts and cardiomyocytes is emerging as a crucial platform to help our understanding and, importantly, to allow the development of effective interventions sufficient to minimize cardiac damage and dysfunction after injury.
Highlights
Edited by: JeanSébastien Silvestre, Institut National de la Santé et de la Recherche Médicale (INSERM), France
Recent evidence implies that resident non-cardiomyocytes, fibroblasts and macrophages -pillars of the innate immunity- form part of the inflammatory response and decisively affect the repair process following a cardiac insult
The interplay of innate immune cells with cardiac fibroblasts and cardiomyocytes is emerging as a crucial platform to help our understanding and, importantly, to allow the development of effective interventions sufficient to minimize cardiac damage and dysfunction after injury
Summary
The first differentiated myocardial cells appear in cardiac crescent at embryonic day E7.5. A similar situation in humans has been sporadically reported [33], conforming to a broader scar-less repair ability lost during development [34] This ability, is not limitless given that apical resection exceeding 15% of neonatal mouse tissue fails to regenerate [35]. In contrast to fetal heart that is comprised by mononuclear cardiomyocytes, the majority of the cardiomyocytes in the adult mouse are bi-nucleated [26] and the extent of bi-nucleation negatively correlates with cardiomyocyte’s ability to proliferate and recover cardiac tissue following an injury [45]. Even in the absence of injury, changes in the stiffness of the extracellular matrix surrounding the cardiomyocytes that occur during the first days of life, may impede the ability of cardiomyocytes to proliferate and the capacity of the cardiac tissue to repair following an insult [38]. Cardiac stromal cells and macrophages, pivotal cellular determinants of the myocardial extracellular milieu, and their interactions with cardiomyocytes have lately attracted much attention as potential targets of intervention to improve cardiac repair
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