Animal models to study cardiac regeneration

Abstract

Permanent fibrosis and chronic deterioration of heart function in human patientsfollowing myocardial infarction present a major healthcare burden worldwide. In contrast to the restricted potential for cellular and functional regeneration of the adult mammalian heart, a robust capacity for cardiac regeneration is seen during the during the neonatal period in mammals as well as in the adults of many fish and amphibian species. However, we lack a complete understanding as to why cardiac regeneration takes place more efficiently in some species than in others. The capacity of the heart to regenerate following injury is controlled by a complex network of cellular and molecular mechanisms that form a regulatory landscape, either permitting or restricting regeneration. In this Review, we provide an overview of the diverse array of vertebrates that have been studied for their cardiac regenerative potential and discuss differential heart regeneration outcomes in closely related species. Additionally, we summarize current knowledge about the core mechanisms that regulate cardiac regeneration across vertebrate species. [H1] IntroductionCardiovascular disease continues to be one of the major causes of death worldwide 1 .Although the survival rate for myocardial infarction (MI) -the death of heart muscle tissue due to a lack of oxygen caused by the disruption of coronary blood flow 2 -has been steadily

ptx3a+ fibroblast/epicardial cells provide a transient macrophage niche to promote heart regeneration

“… 87 After heart injury, inflammatory and reparative phases of the immune response are suggested to be crucial for cardiac regeneration. 88 Our results with ptx3a + cells and macrophages further suggest that activated Fb/Epi cells play pivotal roles in modulating and balancing these two phases to enable robust regeneration. In this study, we also analyzed the scRNA-seq datasets in regenerating zebrafish and neonatal mice hearts and identified upregulation of macrophage-regulating signals like Csf1 family members in Fb/Epi cells.…”

Metabolic Reprogramming: A Byproduct or a Driver of Cardiomyocyte Proliferation?

“…9 When the left ventricular apex of a postnatal day 1 (P1) mouse is excised, surviving cardiomyocytes proliferate to repair the injury and cardiac function is fully restored after 8 weeks. 10 If apical resection is performed in P7 mice or in adult mice, the tissue is not regenerated but is replaced by scar tissue. Therefore, during the first week after birth neonatal cardiomyocytes transition from a proliferative to a quiescent state.…”