The Zebrafish Cardiac Endothelial Cell—Roles in Development and Regeneration

Abstract

In zebrafish, the spatiotemporal development of the vascular system is well described due to its stereotypical nature. However, the cellular and molecular mechanisms orchestrating post-embryonic vascular development, the maintenance of vascular homeostasis, or how coronary vessels integrate into the growing heart are less well studied. In the context of cardiac regeneration, the central cellular mechanism by which the heart regenerates a fully functional myocardium relies on the proliferation of pre-existing cardiomyocytes; the epicardium and the endocardium are also known to play key roles in the regenerative process. Remarkably, revascularisation of the injured tissue occurs within a few hours after cardiac damage, thus generating a vascular network acting as a scaffold for the regenerating myocardium. The activation of the endocardium leads to the secretion of cytokines, further supporting the proliferation of the cardiomyocytes. Although epicardium, endocardium, and myocardium interact with each other to orchestrate heart development and regeneration, in this review, we focus on recent advances in the understanding of the development of the endocardium and the coronary vasculature in zebrafish as well as their pivotal roles in the heart regeneration process.

New developments in the biology of fibroblast growth factors

“…In zebrafish amputation-induced heart injury, FGF signaling is important for neovascularization of the regenerating myocardium through ERK activation in ECs (Lowe et al, 2021). Additionally, following heart injury, the number of cardiomyocytes with activated FGFR-induced AKT signaling was increased.…”

Endocardial-Myocardial Interactions During Early Cardiac Differentiation and Trabeculation

“…Endocardial Tie2 plays complimentary roles during ventricular chamber trabeculation by promoting endocardial proliferation and sprouting, while preventing myocardial hypertrabeculation through suppression of retinoic acid signaling within cardiomyocytes. Beyond this, endocardial cells have roles in coronary vascular development and in haematopoiesis, which suggests that they have roles during heart regeneration and could provide novel progenitors for mural cells of the heart ( 10 , 107 ). Thus, the endocardium is a promising target for therapeutic intervention both to maintain homeostasis within the heart and to stimulate cardiomyocyte replenishment during cardiac disease or injury.…”

Advances in Cardiac Development and Regeneration Using Zebrafish as a Model System for High-Throughput Research

“…In addition to developmental gene regulatory networks, considerable impact of epigenetics [17], distinct cell types, and signaling pathways require more thorough investigations using high-throughput technologies. For a better understanding of regeneration responses so that human cardiac injuries can be addressed, further focus is needed on the regeneration microenvironment [19,22] and cellular roles [150][151][152][153]. These discoveries may, in turn, illuminate new pathways for the early diagnosis of damage to cardiac tissue as occurs in heart disease, such as through the identification of relevant promoters [50], enhancers [50,68], and transcription factors [114,135], as well as new methods of treatment to encourage regeneration of cardiac tissue.…”