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17 pages, 1698 KB  
Review
Making Mobile Leaflets: Biomechanical Forces in Atrioventricular Valve Formation
by Anji Yang and Renee Wei-Yan Chow
Cells 2026, 15(6), 562; https://doi.org/10.3390/cells15060562 - 20 Mar 2026
Viewed by 732
Abstract
Atrioventricular valves prevent the backward flow of blood from the ventricles to the atria and are essential for the efficient pumping of blood throughout the body. Errors in development can lead to congenital atrioventricular valve disease. Atrioventricular valve formation is a multi-step process [...] Read more.
Atrioventricular valves prevent the backward flow of blood from the ventricles to the atria and are essential for the efficient pumping of blood throughout the body. Errors in development can lead to congenital atrioventricular valve disease. Atrioventricular valve formation is a multi-step process that involves endocardial cushion formation, valve progenitor cell proliferation, valve sinus formation, valve elongation, and extracellular matrix remodeling. Increasing evidence suggests that hemodynamic cues are required across multiple steps. Here, we compare atrioventricular valve formation in different in vivo models and review how biomechanical forces regulate atrioventricular valve formation. Full article
(This article belongs to the Section Cells of the Cardiovascular System)
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19 pages, 4487 KB  
Article
Design and Performance Evaluation of Car Seat Heat Pump for Electric Vehicles
by Alfarabi Habil Muhammad, Fauzan, Faris Zaiem Al Hakiem, HyunJung Kim, Sung Hoon Park and Young Soo Chang
Energies 2025, 18(23), 6197; https://doi.org/10.3390/en18236197 - 26 Nov 2025
Cited by 1 | Viewed by 1041
Abstract
This study proposes and evaluates a car seat-integrated heat pump as localized air conditioning system for electric vehicles (EVs). The proposed system uses R1234yf and comprises a compressor, microchannel heat exchangers, an electronic expansion valve, and a four-way reversing valve for bidirectional operation, [...] Read more.
This study proposes and evaluates a car seat-integrated heat pump as localized air conditioning system for electric vehicles (EVs). The proposed system uses R1234yf and comprises a compressor, microchannel heat exchangers, an electronic expansion valve, and a four-way reversing valve for bidirectional operation, delivering conditioned air through the internal seat ducts to the cushion and backrest. A horizontal twin-rotary compressor was developed, which exhibits high isentropic and volumetric efficiencies. The compact module, with a height of 145 mm, a width of 330 mm, a length of 484 mm, and a mass of 20 kg, can be installed under the seat while satisfying the standard SgRP/H30 envelope constraints. Testing was conducted in controlled environmental chambers across representative operating conditions with various airflow rates at different temperatures of 30 °C and 35 °C for cooling and 7 °C and 15 °C for heating. At a typical compressor speed of 4000 rpm, the proposed system achieved coefficient of performance (COP) values of 3.5–5.5 and 4.5–8 in cooling and heating modes and cooling and heating capacities of 650–900 W and 400–600 W, respectively. Concentrating thermal control at the seat is expected to provide rapid, occupant-level cooling/heating with favorable efficiency, indicating a practical path to EV energy savings and thermal comfort. Full article
(This article belongs to the Section J: Thermal Management)
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15 pages, 1896 KB  
Case Report
Pathogenesis of Cardiac Valvular Hemangiomas: A Case Report and Literature Review
by Kimberly-Allisya Neeter, Catalin-Bogdan Satala, Daniela Mihalache, Alexandru-Stefan Neferu, Gabriela Patrichi, Carmen Elena Opris and Simona Gurzu
Int. J. Mol. Sci. 2025, 26(15), 7114; https://doi.org/10.3390/ijms26157114 - 23 Jul 2025
Cited by 1 | Viewed by 1527
Abstract
Valvular hemangiomas are uncommon vascular anomalies that appear on the surface of heart valves. They can cause an array of non-specific symptoms and are consequently rarely diagnosed, with only 31 such cases (including the present one) reported to date in the literature; the [...] Read more.
Valvular hemangiomas are uncommon vascular anomalies that appear on the surface of heart valves. They can cause an array of non-specific symptoms and are consequently rarely diagnosed, with only 31 such cases (including the present one) reported to date in the literature; the present case is the first report of an arteriovenous hemangioma with a tricuspid localization. During the preoperative echocardiographic examination for a ventricular septal defect, a mass was incidentally discovered on the tricuspid valve of a 9-month-old infant. The involved leaflet was surgically removed and sent to the pathology department for analysis and subsequently diagnosed as an arteriovenous hemangioma. The patient recovered well, with no local tumor recurrence or other complications. The microscopic examination showed multiple blood vessels which stained positive for the endothelial markers CD31 and CD34 and which did not express D2-40, normally found in lymphatic endothelia. Surprisingly, endothelial cells lining the vessels also showed positivity for SMA, a mesenchymal cell marker, indicating a possible involvement of endothelial-to-mesenchymal transition and its opposite process, mesenchymal-to-endothelial transition, in the pathogenesis of these vascular anomalies. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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16 pages, 4956 KB  
Article
Dynamic Characterization and Parametric Optimization of Secondary Cushioned Pump Valves in Drilling Systems: A 3D Transient Fluid–Structure Interaction Study
by Yi Wu and Yongjun Hou
Appl. Sci. 2025, 15(10), 5431; https://doi.org/10.3390/app15105431 - 13 May 2025
Cited by 2 | Viewed by 1397
Abstract
The dynamic response of pump valve motion directly influences the volumetric efficiency of drilling pumps and serves as a critical factor in performance enhancement. This study presents a coupled fluid–structure interaction (FSI) analysis of a novel secondary cushioned pump valve for drilling systems. [...] Read more.
The dynamic response of pump valve motion directly influences the volumetric efficiency of drilling pumps and serves as a critical factor in performance enhancement. This study presents a coupled fluid–structure interaction (FSI) analysis of a novel secondary cushioned pump valve for drilling systems. A validated 3D transient numerical model, integrating piston–valve kinematic coupling and clearance threshold modeling, was developed to resolve the dynamic interactions between reciprocating mechanisms and turbulent flow fields. The methodology addresses critical limitations in conventional valve closure simulations by incorporating a geometrically adaptive mesh refinement strategy while maintaining computational stability. Transient velocity profiles confirm complete sealing integrity with near-zero leakage (<0.01 m/s), while a 39.3 MPa inter-pipeline pressure differential induces 16% higher jet velocities in suction valves compared to discharge counterparts. The secondary cushioned valve design reduces closure hysteresis by 22%, enhancing volumetric efficiency under rated conditions. Parametric studies reveal structural dominance, with increases in cylindrical spring stiffness lowering discharge valve lift by 7.2% and velocity amplitude by 2.74%, while wave spring optimization (24% stiffness enhancement) eliminates pressure decay and reduces perturbations by 90%. Operational sensitivity analysis demonstrates stroke frequency as a critical failure determinant: elevating speed from 90 to 120 rpm amplifies suction valve peak velocity by 59.87% and initial closing shock by 129.07%. Transient flow simulations validate configuration-dependent performance, showing 6.3 ± 0.1% flow rate deviations from theoretical predictions (Qt_max = 40.0316 kg/s) due to kinematic hysteresis. This study establishes spring parameter modulation as a key strategy for balancing flow stability and mitigating cushioning-induced oscillations. These findings provide actionable insights for optimizing high-pressure pump systems through hysteresis control and parametric adaptation. Full article
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22 pages, 1749 KB  
Article
Assessing the Critical Factors Leading to the Failure of the Industrial Pressure Relief Valve Through a Hybrid MCDM-FMEA Approach
by Pradnya Kuchekar, Ajay S. Bhongade, Ateekh Ur Rehman and Syed Hammad Mian
Machines 2024, 12(11), 820; https://doi.org/10.3390/machines12110820 - 17 Nov 2024
Cited by 10 | Viewed by 3536
Abstract
Industrial pressure relief valves must function reliably and effectively to protect pressurized systems from excessive pressure conditions. These valves are essential safety devices that act as cushions to protect piping systems, equipment, and vessels from the risks of high pressure, which can cause [...] Read more.
Industrial pressure relief valves must function reliably and effectively to protect pressurized systems from excessive pressure conditions. These valves are essential safety devices that act as cushions to protect piping systems, equipment, and vessels from the risks of high pressure, which can cause damage or even explosions. The objectives of this study were to minimize valve failures, decrease the number of rejected valves in the production line, and enhance the overall quality of pressure relief valves. This work introduces an integrated quality improvement methodology known as the hybrid multi-criteria decision-making (MCDM)—failure mode and effects analysis (FMEA) approach. This approach is based on prioritizing crucial factors for any failure modes in the industrial setting. The presented case study demonstrates the application of a hybrid approach for identifying the fundamental causes of industrial pressure relief valve failure modes and malfunctions. This investigation highlights the applicability of FMEA as a methodology for determining causes and executing remedial actions to keep failures from happening again. FMEA helps uncover the underlying causes of industrial pressure relief valve failures, while the integration of the hybrid MCDM methodology enables the application of four integrated MCDM methods to identify crucial factors. The adopted model addresses the shortcomings of the conventional FMEA by accurately analyzing the relationships between the risk factors and by utilizing several MCDM methods to rank failure modes. Following the application of the adopted methodology, it was discovered that the high-risk failure modes for the pressure relief valve included misalignment of wire, normal wear/aging, rejection of machined parts, mismatch of mating parts, and corrosion. Therefore, risk managers should prioritize developing improvement strategies for these five failure modes. Similarly, failures comprising debris, delayed valve opening, internal leakage, premature valve opening, and burr foreign particles were determined as second essential groups for improvement. Full article
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15 pages, 1798 KB  
Article
Hippo Signaling Mediates TGFβ-Dependent Transcriptional Inputs in Cardiac Cushion Mesenchymal Cells to Regulate Extracellular Matrix Remodeling
by Mrinmay Chakrabarti, Ahad Chattha, Abhijith Nair, Kai Jiao, Jay D. Potts, Lianming Wang, Scotty Branch, Shea Harrelson, Saeed Khan and Mohamad Azhar
J. Cardiovasc. Dev. Dis. 2023, 10(12), 483; https://doi.org/10.3390/jcdd10120483 - 4 Dec 2023
Cited by 6 | Viewed by 3433
Abstract
The transforming growth factor beta (TGFβ) and Hippo signaling pathways are evolutionarily conserved pathways that play a critical role in cardiac fibroblasts during embryonic development, tissue repair, and fibrosis. TGFβ signaling and Hippo signaling are also important for cardiac cushion remodeling and septation [...] Read more.
The transforming growth factor beta (TGFβ) and Hippo signaling pathways are evolutionarily conserved pathways that play a critical role in cardiac fibroblasts during embryonic development, tissue repair, and fibrosis. TGFβ signaling and Hippo signaling are also important for cardiac cushion remodeling and septation during embryonic development. Loss of TGFβ2 in mice causes cardiac cushion remodeling defects resulting in congenital heart disease. In this study, we used in vitro molecular and pharmacologic approaches in the cushion mesenchymal cell line (tsA58-AVM) and investigated if the Hippo pathway acts as a mediator of TGFβ2 signaling. Immunofluorescence staining showed that TGFβ2 induced nuclear translocation of activated SMAD3 in the cushion mesenchymal cells. In addition, the results indicate increased nuclear localization of Yes-associated protein 1 (YAP1) following a similar treatment of TGFβ2. In collagen lattice formation assays, the TGFβ2 treatment of cushion cells resulted in an enhanced collagen contraction compared to the untreated cushion cells. Interestingly, verteporfin, a YAP1 inhibitor, significantly blocked the ability of cushion cells to contract collagen gel in the absence or presence of exogenously added TGFβ2. To confirm the molecular mechanisms of the verteporfin-induced inhibition of TGFβ2-dependent extracellular matrix (ECM) reorganization, we performed a gene expression analysis of key mesenchymal genes involved in ECM remodeling in heart development and disease. Our results confirm that verteporfin significantly decreased the expression of α-smooth muscle actin (Acta2), collagen 1a1 (Col1a1), Ccn1 (i.e., Cyr61), and Ccn2 (i.e., Ctgf). Western blot analysis indicated that verteporfin treatment significantly blocked the TGFβ2-induced activation of SMAD2/3 in cushion mesenchymal cells. Collectively, these results indicate that TGFβ2 regulation of cushion mesenchymal cell behavior and ECM remodeling is mediated by YAP1. Thus, the TGFβ2 and Hippo pathway integration represents an important step in understanding the etiology of congenital heart disease. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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10 pages, 4304 KB  
Proceeding Paper
Implementation of an Electro-Hydraulic Drive Unit with Two Control Variables in a Drawing Cushion Application
by Willy Reichert, Alexander Leonhard, Thomas Päßler, Robin Kurth and Steffen Ihlenfeldt
Eng. Proc. 2022, 26(1), 18; https://doi.org/10.3390/engproc2022026018 - 15 Nov 2022
Cited by 2 | Viewed by 2020
Abstract
Forming machines and their subsystems, e.g., the drawing cushion in sheet metal-forming machines, pose high power as well as precision requirements in both the positioning and the force, which are directly linked to the quality of the produced part. In addition to ensuring [...] Read more.
Forming machines and their subsystems, e.g., the drawing cushion in sheet metal-forming machines, pose high power as well as precision requirements in both the positioning and the force, which are directly linked to the quality of the produced part. In addition to ensuring quality, energy efficiency becomes increasingly important. The first step towards energy efficiency is utilizing direct drives, which reduce the energy consumed by the machine significantly, compared to valve-controlled applications. Additional potential for energy loss reduction lies in the implementation of a direct drive unit with the two control variables, motor speed and displacement volume. The control variable distribution results in an influence on the dynamics of the system. This influence is studied in this paper. Full article
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9 pages, 1389 KB  
Editorial
Introduction to Special Issue “Leaders in Cardiovascular Research, Dedicated to the Memory of Professor Adriana Gittenberger-de Groot”
by Edi Gittenberger, Robert E. Poelmann and Monique R. M. Jongbloed
J. Cardiovasc. Dev. Dis. 2022, 9(4), 92; https://doi.org/10.3390/jcdd9040092 - 23 Mar 2022
Viewed by 3511
Abstract
This Introduction provides both a short reflection on the scientific career of Adriana Gittenberger-de Groot and an overview of the papers that form the basis of this Special Issue giving them a proper perspective. The papers have as a central focus the outflow [...] Read more.
This Introduction provides both a short reflection on the scientific career of Adriana Gittenberger-de Groot and an overview of the papers that form the basis of this Special Issue giving them a proper perspective. The papers have as a central focus the outflow tract, and include contributions on development and pathology of the ventricles including AV valves, as well as developmental and pathomorphological aspects of the great arteries including semilunar valves and coronary arteries. Full article
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15 pages, 6838 KB  
Article
Research on Steering Vibration Analysis of Wheel Loader and Cushion Valve Design
by Tongjian Wang, Yichuan Wang, Lihui Zhu, Zhenling Zhi, Zongjian Liu and Rencheng Li
Energies 2022, 15(3), 805; https://doi.org/10.3390/en15030805 - 22 Jan 2022
Cited by 2 | Viewed by 4372
Abstract
At present, the wheel loaders on the market have steering vibration problems, which can be summarized as follows: the front frame and the cab vibrate violently at the beginning and at the end of steering. This paper analyzed the steering vibration mechanism by [...] Read more.
At present, the wheel loaders on the market have steering vibration problems, which can be summarized as follows: the front frame and the cab vibrate violently at the beginning and at the end of steering. This paper analyzed the steering vibration mechanism by collecting the pressure at different positions of the hydraulic steering system and AMESim simulation. A cushion valve was designed to solve the problem of steering vibration. Finally, the prototype test was carried out and it was concluded that the cushion valve reduced the steering pressure starting shock by 50%, the stop vibration was reduced by 75%, and the suction problem no longer occurred. Further, the analysis provides theoretical and experimental basis for research on the steering system of loaders, and also provides new ideas for the design and optimization of vehicle steering systems. Full article
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15 pages, 10712 KB  
Article
Energy Savings Analysis for Operation of Steam Cushion System for Sensible Thermal Energy Storages
by Ryszard Zwierzchowski, Olgierd Niemyjski and Marcin Wołowicz
Energies 2022, 15(1), 286; https://doi.org/10.3390/en15010286 - 1 Jan 2022
Cited by 2 | Viewed by 2524
Abstract
The paper presents an analytical discussion of how to improve the energy efficiency of the steam cushion system operation for a Thermal Energy Storage (TES) tank. The EU’s green deal 2050 target policy requires an increase in the energy efficiency of energy production [...] Read more.
The paper presents an analytical discussion of how to improve the energy efficiency of the steam cushion system operation for a Thermal Energy Storage (TES) tank. The EU’s green deal 2050 target policy requires an increase in the energy efficiency of energy production and use, as well as an increase in the share of renewable energy in the overall energy production balance. The use of energy-efficient TES is considered as one of the most important technologies to achieve the objectives of this EU policy. The analyses presented in the paper of energy-efficient operation of steam cushion (SC) systems were carried out by using operational data received from three District Heating Systems (DHSs) that supply heat and electricity to one of the largest cities in Poland and are equipped with the TES systems. These three analyzed TESs differ in capacities from 12,800 to 30,400 m3, tank diameters from 21 to 30 m and shell height from 37 to 48.2 m. The main purpose of using a steam cushion system in the TES tank is to protect the water stored in it against the absorption of oxygen from the surrounding atmospheric air through the surge chamber and safety valves located on the roof of the tank. The technical solutions presented here for the upper orifice for charging and discharging hot water into/from the tank and the suction pipe for circulating water allow to us achieve significant energy savings in the steam cushion systems. Both the upper orifice and the end of suction pipe are movable through the use of pontoons. Thanks to the use of this technical solution, a stable insulating water layer is created above the upper orifice in the upper part of the TES tank, where convective and turbulent transport of heat from the steam cushion space to the hot water stored in the tank is significantly limited. Ultimately, this reduces the heat flux by approximately 90% when compared to the classic technical solutions of steam cushion systems in TES tanks, i.e., for the upper orifice and circulation water pipe. The simplified analysis presented in the paper and comparison of its results with experimental data for heat flow from the steam cushion space to hot water stored in the upper part of the TES tank fully confirms the usefulness of the heat-flow models used. Full article
(This article belongs to the Special Issue High-Efficiency Thermal-Storage Devices and Systems)
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19 pages, 6433 KB  
Article
Ventricular Septation and Outflow Tract Development in Crocodilians Result in Two Aortas with Bicuspid Semilunar Valves
by Robert E. Poelmann, Adriana C. Gittenberger-de Groot, Charissa Goerdajal, Nimrat Grewal, Merijn A. G. De Bakker and Michael K. Richardson
J. Cardiovasc. Dev. Dis. 2021, 8(10), 132; https://doi.org/10.3390/jcdd8100132 - 15 Oct 2021
Cited by 12 | Viewed by 4209
Abstract
Background: The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy, however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortas originating from either the right or left [...] Read more.
Background: The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy, however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortas originating from either the right or left ventricular cavity. Mixing of blood in crocodilians cannot occur at the ventricular level as in other reptiles but instead takes place at the aortic root level by a shunt, the foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods: Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris were studied histologically. Results and Conclusions: The outflow tract septation complex can be divided into two components. The aorto-pulmonary septum divides the pulmonary trunk from both aortas, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion. Full article
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18 pages, 4273 KB  
Review
Role of the Epicardium in the Development of the Atrioventricular Valves and Its Relevance to the Pathogenesis of Myxomatous Valve Disease
by Renélyn Wolters, Ray Deepe, Jenna Drummond, Andrew B. Harvey, Emilye Hiriart, Marie M. Lockhart, Maurice J. B. van den Hoff, Russell A. Norris and Andy Wessels
J. Cardiovasc. Dev. Dis. 2021, 8(5), 54; https://doi.org/10.3390/jcdd8050054 - 12 May 2021
Cited by 5 | Viewed by 5601
Abstract
This paper is dedicated to the memory of Dr. Adriana “Adri” Gittenberger-de Groot and in appreciation of her work in the field of developmental cardiovascular biology and the legacy that she has left behind. During her impressive career, Dr. Gittenberger-de Groot studied many [...] Read more.
This paper is dedicated to the memory of Dr. Adriana “Adri” Gittenberger-de Groot and in appreciation of her work in the field of developmental cardiovascular biology and the legacy that she has left behind. During her impressive career, Dr. Gittenberger-de Groot studied many aspects of heart development, including aspects of cardiac valve formation and disease and the role of the epicardium in the formation of the heart. In this contribution, we review some of the work on the role of epicardially-derived cells (EPDCs) in the development of the atrioventricular valves and their potential involvement in the pathogenesis of myxomatous valve disease (MVD). We provide an overview of critical events in the development of the atrioventricular junction, discuss the role of the epicardium in these events, and illustrate how interfering with molecular mechanisms that are involved in the epicardial-dependent formation of the atrioventricular junction leads to a number of abnormalities. These abnormalities include defects of the AV valves that resemble those observed in humans that suffer from MVD. The studies demonstrate the importance of the epicardium for the proper formation and maturation of the AV valves and show that the possibility of epicardial-associated developmental defects should be taken into consideration when determining the genetic origin and pathogenesis of MVD. Full article
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16 pages, 1240 KB  
Review
Outflow Tract Formation—Embryonic Origins of Conotruncal Congenital Heart Disease
by Sonia Stefanovic, Heather C. Etchevers and Stéphane Zaffran
J. Cardiovasc. Dev. Dis. 2021, 8(4), 42; https://doi.org/10.3390/jcdd8040042 - 9 Apr 2021
Cited by 34 | Viewed by 9274
Abstract
Anomalies in the cardiac outflow tract (OFT) are among the most frequent congenital heart defects (CHDs). During embryogenesis, the cardiac OFT is a dynamic structure at the arterial pole of the heart. Heart tube elongation occurs by addition of cells from pharyngeal, splanchnic [...] Read more.
Anomalies in the cardiac outflow tract (OFT) are among the most frequent congenital heart defects (CHDs). During embryogenesis, the cardiac OFT is a dynamic structure at the arterial pole of the heart. Heart tube elongation occurs by addition of cells from pharyngeal, splanchnic mesoderm to both ends. These progenitor cells, termed the second heart field (SHF), were first identified twenty years ago as essential to the growth of the forming heart tube and major contributors to the OFT. Perturbation of SHF development results in common forms of CHDs, including anomalies of the great arteries. OFT development also depends on paracrine interactions between multiple cell types, including myocardial, endocardial and neural crest lineages. In this publication, dedicated to Professor Andriana Gittenberger-De Groot and her contributions to the field of cardiac development and CHDs, we review some of her pioneering studies of OFT development with particular interest in the diverse origins of the many cell types that contribute to the OFT. We also discuss the clinical implications of selected key findings for our understanding of the etiology of CHDs and particularly OFT malformations. Full article
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15 pages, 5668 KB  
Article
Myocardial TGFβ2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development
by Aniket Bhattacharya, Nadia Al-Sammarraie, Mengistu G. Gebere, John Johnson, John F. Eberth and Mohamad Azhar
J. Cardiovasc. Dev. Dis. 2021, 8(3), 26; https://doi.org/10.3390/jcdd8030026 - 2 Mar 2021
Cited by 8 | Viewed by 4229
Abstract
Among the three transforming growth factor beta (TGFβ) ligands, TGFβ2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, [...] Read more.
Among the three transforming growth factor beta (TGFβ) ligands, TGFβ2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, including mitral valve prolapse (MVP) with or without regurgitation. Tgfb2 germline knockout fetuses exhibit multiple cardiac defects but the role of myocardial-TGFβ2 in heart development is yet to be elucidated. Here, myocardial Tgfb2 conditional knockout (CKO) embryos were generated by crossing Tgfb2flox mice with Tgfb2+/−; cTntCre mice. Tgfb2flox/− embryos were normal, viable. Cell fate mapping was done using dual-fluorescent mT/mG+/− mice. Cre-mediated Tgfb2 deletion was assessed by genomic PCR. RNAscope in situ hybridization was used to detect the loss of myocardial Tgfb2 expression. Histological, morphometric, immunohistochemical, and in situ hybridization analyses of CKOs and littermate controls at different stages of heart development (E12.5–E18.5) were used to determine the role of myocardium-derived TGFβ2 in atrioventricular (AV) cushion remodeling and myocardial development. CKOs exhibit a thin ventricular myocardium, AV cushion remodeling defects and developed incomplete AV septation defects. The loss of myocardial Tgfb2 resulted in impaired cushion maturation and dysregulated cell death. Phosphorylated SMAD2, a surrogate for TGFβ signaling, was “paradoxically” increased in both AV cushion mesenchyme and ventricular myocardium in the CKOs. Our results indicate that TGFβ2 produced by cardiomyocytes acting as cells autonomously on myocardium and via paracrine signaling on AV cushions are required for heart development. Full article
(This article belongs to the Special Issue Mitral Valve Development and Disease)
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16 pages, 16725 KB  
Review
Atrioventricular Septal Defect: What Is in a Name?
by Michael Rigby
J. Cardiovasc. Dev. Dis. 2021, 8(2), 19; https://doi.org/10.3390/jcdd8020019 - 15 Feb 2021
Cited by 17 | Viewed by 9677
Abstract
Robert Anderson has made a huge contribution to almost all aspects of morphology and understanding of congenital cardiac malformations, none more so than the group of anomalies that many of those in the practice of paediatric cardiology and adult congenital heart disease now [...] Read more.
Robert Anderson has made a huge contribution to almost all aspects of morphology and understanding of congenital cardiac malformations, none more so than the group of anomalies that many of those in the practice of paediatric cardiology and adult congenital heart disease now call ‘Atrioventricular Septal Defect’ (AVSD). In 1982, with Anton Becker working in Amsterdam, their hallmark ‘What’s in a name?’ editorial was published in the Journal of Thoracic and Cardiovascular Surgery. At that time most described the group of lesions as ‘atrioventricular canal malformation’ or ‘endocardial cushion defect’. Perhaps more significantly, the so-called ostium primum defect was thought to represent a partial variant. It was also universally thought, at that time, that the left atrioventricular valve was no more than a mitral valve with a cleft in the aortic leaflet. In addition to this, lesions such as isolated cleft of the mitral valve, large ventricular septal defects opening to the inlet of the right and hearts with straddling or overriding tricuspid valve were variations of the atrioventricular canal malformation. Anderson and Becker emphasised the differences between the atrioventricular junction in the normal heart and those with a common junction for which they recommended the generic name, ‘atrioventricular septal defect’. As I will discuss, over many years, they continued to work with clinical cardiologists and cardiac surgeons to refine diagnostic criteria and transform the classification and understanding of this complex group of anomalies. Their emphasis was always on accurate diagnosis and communication, which is conveyed in this review. Full article
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