Endocardium is critically important for proper function of the cardiovascular system. Not only does endocardium connect the heart to blood vasculature, it also plays an important role in heart morphogenesis, valve formation, and ventricular trabeculation. The extracellular protein Fibronectin (Fn1) promotes endocardial differentiation, but the signaling pathways downstream of Fn1 that regulate endocardial development are not understood. Here, we analyzed the role of the Fibronectin receptors Integrin alpha5 (Itga5) and Integrin alpha4 (Itga4) in zebrafish heart development. We show that itga5 mRNA is expressed in both endocardium and myocardium during early stages of heart development. Through analysis of both itga5 single mutants and itga4;itga5 double mutants, we show that loss of both itga5 and itga4 results in enhanced defects in endocardial differentiation and morphogenesis compared to loss of itga5 alone. Loss of both itga5 and itga4 results in cardia bifida and severe myocardial morphology defects. Finally, we find that loss of itga5 and itga4 results in abnormally narrow anterior endodermal sheet morphology. Together, our results support a model in which Itga5 and Itga4 cooperate to promote endocardial differentiation, medial migration of endocardial and myocardial cells, and morphogenesis of anterior endoderm.
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http://dx.doi.org/10.1016/j.ydbio.2020.06.006 | DOI Listing |
Dev Growth Differ
January 2025
Division of Anatomy and Developmental Biology, Department of Anatomy, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Sonic Hedgehog (Shh), encoding an extracellular signaling molecule, is vital for heart development. Shh null mutants show congenital heart disease due to left-right asymmetry defects stemming from functional anomaly in the midline structure in mice. Shh signaling is also known to affect cardiomyocyte differentiation, endocardium development, and heart morphogenesis, particularly in second heart field (SHF) cardiac progenitor cells that contribute to the right ventricle, outflow tract, and parts of the atrium.
View Article and Find Full Text PDFJ Ultrasound Med
January 2025
Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Objectives: The size, shape, and contractility of the heart's atrial chambers have not been evaluated in fetuses with growth restriction (FGR) or who are small-for-gestational-age (SGA) as defined by the Delphi consensus protocol. This study aimed to examine the atrial chambers using speckle tracking analysis to identify any changes that may be specific for either growth disturbance.
Methods: Sixty-three fetuses were evaluated with an estimated fetal weight <10th percentile who were classified as FGR or SGA based on the Delphi consensus protocol.
Catheter Cardiovasc Interv
December 2024
Heart Valve Center, San Raffaele Hospital, Milan, Italy.
Functional mitral regurgitation (MR) is associated with increased cardiovascular morbidity and mortality and over the past decade, the diagnosis of atrial functional mitral regurgitation (aFMR) has been increasingly observed in the elderly, especially in those with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). Annular enlargement, perturbations of annular contraction, and atriogenic leaflet tethering distinguish the pathophysiology of aFMR from the one of ventricular origin. However, no consensus provides recommendations regarding the differential diagnosis and the subsequent management of aFMR.
View Article and Find Full Text PDFArkh Patol
December 2024
Cancer Research Institute, branch of Tomsk National Research Medical Center, Tomsk, Russia.
Cardiac myxoma in its morphology is a typical benign tumor, meanwhile, the fact of its localization in the heart chamber, directly in the constant blood flow, largely determines the clinical behavior of this neoplasm, which is often manifested by the development of characteristics that formally determine the aggressive and even malignant nature of the course. Accordingly, the malignancy of cardiac myxoma is determined more by its clinical behavior (recurrence, multifocality of the lesion, the presence of mechanisms of spread similar to metastasis) rather than by its histological picture. In the structure of primary benign tumors of the heart, myxoma occupies a dominant position and its incidence is up to 85%.
View Article and Find Full Text PDFDevelopment
December 2024
Centre Hospitalier Universitaire Sainte-Justine Research Center, 3175 Chemin de la Côte-Sainte-Catherine, H3T 1C5 Montréal, QC, Canada.
VEGFA administration has been explored as a pro-angiogenic therapy for cardiovascular diseases including heart failure for several years, but with little success. Here, we investigate a different approach to augment VEGFA bioavailability: by deleting the VEGFA decoy receptor VEGFR1 (also known as FLT1), one can achieve more physiological VEGFA concentrations. We find that after cryoinjury, zebrafish flt1 mutant hearts display enhanced coronary revascularization and endocardial expansion, increased cardiomyocyte dedifferentiation and proliferation, and decreased scarring.
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