Endocardial Regulation of Cardiac Development

Abstract

The endocardium is a specialized form of endothelium that lines the inner side of the heart chambers and plays a crucial role in cardiac development. While comparatively less studied than other cardiac cell types, much progress has been made in understanding the regulation of and by the endocardium over the past two decades. In this review, we will summarize what is currently known regarding endocardial origin and development, the relationship between endocardium and other cardiac cell types, and the various lineages that endocardial cells derive from and contribute to. These processes are driven by key molecular mechanisms such as Notch and BMP signaling. These pathways in particular have been well studied, but other signaling pathways and mechanical cues also play important roles. Finally, we will touch on the contribution of stem cell modeling in combination with single cell sequencing and its potential translational impact for congenital heart defects such as bicuspid aortic valves and hypoplastic left heart syndrome. The detailed understanding of cellular and molecular processes in the endocardium will be vital to further develop representative stem cell-derived models for disease modeling and regenerative medicine in the future.

Rapid Progression of Heterotopic Ossification in Severe Variant of Fibrodysplasia Ossificans Progressiva with p.Arg258Gly in ACVR1: A Case Report and Review of Clinical Phenotypes

“…BMP signaling is also implicated in development of the heart [ 14 ]. Clinically, some variants of ACVR1 were reported to cause congenital heart defects, but not FOP [ 15 ].…”

Isolation and Characterization of Porcine Endocardial Endothelial Cells

“…EECs demonstrate their fascinating plasticity during cardiogenesis when they undergo endothelial-to-mesenchymal transition (EndMT) to contribute to heart valve formation (18,23). After development, EECs serve as the inner lining of the heart and regulate oxygen and nutrient supply, mediate immune cell trafficking, and secrete vital signaling molecules to surrounding tissues (9,20,22,24,25). As EECs play an essential role in cardiac formation and function, and dysfunction of EECs has been implicated in several cardiac diseases including congenital valve disease, hypoplastic left heart syndrome, and cardiac hypertrophy (22,(26)(27)(28).…”

Rnf20 shapes the endothelial control of heart morphogenesis and function

“…However little is known about the molecular players safeguarding physiological signaling between these cell types. During embryogenesis, endocardial endothelial cells (ECs) and myocardial precursors arise bilaterally within the mesoderm and through migration and embryo folding coalesce at the ventral midline to form a primitive heart tube consisting of an inner endocardial layer and an outer myocardial layer (Feulner et al, 2022; Tian and Morrisey, 2012). The two layers are separated by a dense layer of extracellular matrix (ECM), termed cardiac jelly, but communicate through paracrine signals.…”

“…On the other hand, it receives and secretes signals that instruct heart morphogenesis and function, e.g. trabeculation, cardiac valve and septum formation, and myocardial compaction, thereby functioning as a crucial signaling interface (Feulner et al, 2022; Kim et al, 2021; Tian and Morrisey, 2012). With the formation of the compact myocardium intramyocardial vessels develop, which also signal to the subjacent cardiomyocytes (CMs) to regulate cardiac growth, contractility and rhythmicity.…”

“…With the formation of the compact myocardium intramyocardial vessels develop, which also signal to the subjacent cardiomyocytes (CMs) to regulate cardiac growth, contractility and rhythmicity. The importance of ECs for heart development has been demonstrated by endothelial-specific gene inactivation of different components of the Notch, vascular endothelial growth factor (VEGF), bone morphogenic protein (BMP), transforming growth factor (TGF), fibroblast growth factor (FGF), Neuregulin-1 (Nrg1)/Erbb2/b4 and angiopoietin-1 signaling pathways (Feulner et al, 2022; Kim et al, 2021; Tian and Morrisey, 2012). However, how signal-dependent transcription is coordinated during heart development is largely unknown.…”