Tie2 regulates endocardial sprouting and myocardial trabeculation

Qu, Xiaomei; Harmelink, Cristina; Baldwin, H. Scott

doi:10.1172/jci.insight.96002

Cited by 21 publications

(40 citation statements)

References 54 publications

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“…The first step is the polarity-dependent OCD, cell orientation, and directional migration of cardiomyocytes in the early myocardium, which contribute to trabecular initiation, resulting in myocardium with multiple-layer cells in mice [13,[36][37][38][39]41]. Subsequently, the endocardial cells burrow into the multiple-layer myocardium and separate cardiomyocytes to form trabeculae [42,43]. After trabecular formation, the myocardium will undergo compaction through gradually compacting inwards from the base to the apex [61,70], and the trabeculae will coalesce with the compact zone to form the thickened compact zone [46].…”

Section: Congenital Lvnc or Acquired Lvncmentioning

confidence: 99%

“…Moreover, perpendicular OCD has contributed to trabecular specification and is responsible for trabecular cardiomyocytes being distinct from the cardiomyocytes in the compact zone [36]. After the trabecular initiation, the myocardium contains multiple layers of cardiomyocytes, and endocardial cells can burrow into the loose cardiomyocytes and separate them to form trabeculae [42,43].…”

Section: Introductionmentioning

confidence: 99%

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Left Ventricular Noncompaction Is Associated with Valvular Regurgitation and a Variety of Arrhythmias

Li-hong

Abdelnasser

et al. 2022

JCDD

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Left ventricular noncompaction (LVNC) is a type of cardiomyopathy characterized anatomically by prominent ventricular trabeculation and deep intertrabecular recesses. The mortality associated with LVNC ranges from 5% to 47%. The etiology of LVNC is yet to be fully understood, although decades have passed since its recognition as a clinical entity globally. Furthermore, critical questions, i.e., whether LVNC represents an acquired pathology or has a congenital origin and whether the reduced contractile function in LVNC patients is a cause or consequence of noncompaction, remain to be addressed. In this study, to answer some of these questions, we analyzed the clinical features of LVNC patients. Out of 9582 subjects screened for abnormal cardiac functions, 45 exhibit the characteristics of LVNC, and 1 presents right ventricular noncompaction (RVNC). We found that 40 patients show valvular regurgitation, 39 manifest reduced systolic contractions, and 46 out of the 46 present different forms of arrhythmias that are not restricted to be caused by the noncompact myocardium. This retrospective examination of LVNC patients reveals some novel findings: LVNC is associated with regurgitation in most patients and arrhythmias in all patients. The thickness ratio of the trabecular layer to compact layer negatively correlates with fractional shortening, and reduced contractility might result from LVNC. This study adds evidence to support a congenital origin of LVNC that might benefit the diagnosis and subsequent characterization of LVNC patients.

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Section: Congenital Lvnc or Acquired Lvncmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Left Ventricular Noncompaction Is Associated with Valvular Regurgitation and a Variety of Arrhythmias

Li-hong

Abdelnasser

et al. 2022

JCDD

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“…Cardiac trabeculation is initiated, at least in zebrafish, by individual CMs delaminating from the compact myocardial wall and protruding into the lumen (Liu et al, 2010; Staudt et al, 2014; Jimenez-Amilburu et al, 2016; Priya et al, 2020). Several studies have reported that the endocardium plays an important role during cardiac trabeculation (Grego-Bessa et al, 2007; Lai et al, 2010; D’Amato et al, 2016; Rasouli and Stainier, 2017; Del Monte-Nieto et al, 2018; Qu et al, 2019). Furthermore, it has recently been shown that EdCs, similar to ECs, undergo sprouting (Del Monte-Nieto et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Mouse and zebrafish embryos lacking the endocardium derived ligand Nrg or the ErbB receptor, which is expressed by the myocardium, fail to form trabeculae (Gassmann et al, 1995; Lee et al, 1995; Meyer and Birchmeier, 1995; Lai et al, 2010; Liu et al, 2010; Rasouli and Stainier, 2017). Furthermore, endocardial Notch signaling (Grego-Bessa et al, 2007; D’Amato et al, 2016; Del Monte-Nieto et al, 2018), angiopoietin 1/Tie2 signaling (Suri et al, 1996; Tachibana et al, 2005; Qu et al, 2019), and semaphorin 3E (Sema3E)/plexinD1 signaling (Sandireddy et al, 2019) are required for cardiac trabeculation in mouse. Of note, genetic deletion of the relevant receptors in the endocardium results in attenuated endocardial sprouting (Qu et al, 2019) and trabeculation defects (Grego-Bessa et al, 2007; D’Amato et al, 2016; Del Monte-Nieto et al, 2018; Qu et al, 2019; Sandireddy et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish

Rittershaus

Priya

et al. 2021

Preprint

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During cardiac development, endocardial cells (EdCs) produce growth factors to promote myocardial morphogenesis and growth. In particular, EdCs produce Neuregulin which is required for ventricular cardiomyocytes (CMs) to seed the multicellular ridges known as trabeculae. Defects in Neuregulin signaling, or in endocardial sprouting towards CMs, cause hypotrabeculation. However, the mechanisms underlying endocardial sprouting remain largely unknown. Here, we first show by live imaging in zebrafish embryos that EdCs interact with CMs via dynamic membrane protrusions. After touching CMs, these protrusions remain in close contact with their target despite the vigorous cardiac contractions. Loss of the CM-derived peptide Apelin, or of the Apelin receptor, which is expressed in EdCs, leads to reduced endocardial sprouting and hypotrabeculation. Mechanistically, Neuregulin signaling requires endocardial protrusions to activate extracellular signal-regulated kinase (Erk) signaling in CMs and trigger their delamination. Altogether, these data show that Apelin signaling dependent endocardial protrusions modulate CM behavior during trabeculation.

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“…Activation of Bmp10 is also independent of EphrinB2 and Nrg1 expression during trabeculation ( Grego-Bessa et al, 2007 ). Following the trabeculae growth, hypertrabeculation is prevented by endocardial Tie2 expression, which inhibits proliferation of cardiomyocytes ( Qu et al, 2019 ). Single-cell analysis of the ligand-receptor pairs between cardiomyocytes and endocardial cells in E10.5 mouse heart also showed that expression of transforming growth factor beta 1 (Tgfb1), previously characterized to inhibit proliferation of cardiomyocytes, was specifically identified in endocardial cells, and expression of its receptors Tgfbr1 and Tgfbr3 was found in cardiomyocytes ( Li et al, 2019 ).…”

Section: Trabeculation and Compaction Of Myocardiummentioning

confidence: 99%

Endothelial-Myocardial Angiocrine Signaling in Heart Development

Kim

Wang

Paik

2021

Front. Cell Dev. Biol.

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Vascular endothelial cells are a multifunctional cell type with organotypic specificity in their function and structure. In this review, we discuss various subpopulations of endothelial cells in the mammalian heart, which spatiotemporally regulate critical cellular and molecular processes of heart development via unique sets of angiocrine signaling pathways. In particular, elucidation of intercellular communication among the functional cell types in the developing heart has recently been accelerated by the use of single-cell sequencing. Specifically, we overview the heterogeneic nature of cardiac endothelial cells and their contribution to heart tube and chamber formation, myocardial trabeculation and compaction, and endocardial cushion and valve formation via angiocrine pathways.

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Tie2 regulates endocardial sprouting and myocardial trabeculation

Cited by 21 publications

References 54 publications

Left Ventricular Noncompaction Is Associated with Valvular Regurgitation and a Variety of Arrhythmias

Left Ventricular Noncompaction Is Associated with Valvular Regurgitation and a Variety of Arrhythmias

Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish

Endothelial-Myocardial Angiocrine Signaling in Heart Development

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