scholarly journals GATA4 Is a Direct Transcriptional Activator of Cyclin D2 and Cdk4 and Is Required for Cardiomyocyte Proliferation in Anterior Heart Field-Derived Myocardium

2008 ◽  
Vol 28 (17) ◽  
pp. 5420-5431 ◽  
Author(s):  
Anabel Rojas ◽  
Sek Won Kong ◽  
Pooja Agarwal ◽  
Brian Gilliss ◽  
William T. Pu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Right Ventricle ◽  
Interventricular Septum ◽  
Cardiomyocyte Proliferation ◽  
Cyclin D2 ◽  
Cell Cycle Genes ◽  
Numerous Cell ◽  
Heart Field ◽  
The Right

ABSTRACT The anterior heart field (AHF) comprises a population of mesodermal progenitor cells that are added to the nascent linear heart to give rise to the majority of the right ventricle, interventricular septum, and outflow tract in mammals and birds. The zinc finger transcription factor GATA4 functions as an integral member of the cardiac transcription factor network in the derivatives of the AHF. In addition to its role in cardiac differentiation, GATA4 is also required for cardiomyocyte replication, although the transcriptional targets of GATA4 required for proliferation have not been previously identified. In the present study, we disrupted Gata4 function exclusively in the AHF and its derivatives. Gata4 AHF knockout mice die by embryonic day 13.5 and exhibit hypoplasia of the right ventricular myocardium and interventricular septum and display profound ventricular septal defects. Loss of Gata4 function in the AHF results in decreased myocyte proliferation in the right ventricle, and we identified numerous cell cycle genes that are dependent on Gata4 by microarray analysis. We show that GATA4 is required for cyclin D2, cyclin A2, and Cdk4 expression in the right ventricle and that the Cyclin D2 and Cdk4 promoters are bound and activated by GATA4 via multiple consensus GATA binding sites in each gene's proximal promoter. These findings establish Cyclin D2 and Cdk4 as direct transcriptional targets of GATA4 and support a model in which GATA4 controls cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes.

scholarly journals Gata4 drives Hh-signaling for second heart field migration and outflow tract development

2018 ◽  
Author(s):  
Jielin Liu ◽  
Henghui Cheng ◽  
Menglan Xiang ◽  
Lun Zhou ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Right Ventricle ◽  
Double Outlet Right Ventricle ◽  
Precursor Cells ◽  
Outflow Tract ◽  
Second Heart Field ◽  
Heart Field ◽  
Hh Signaling ◽  
The Right ◽  
Cardiac Precursor Cells

AbstractDominant mutations of Gata4, an essential cardiogenic transcription factor (TF), cause outflow tract (OFT) defects in both human and mouse. We investigated the molecular mechanism underlying this requirement. Gata4 happloinsufficiency in mice caused OFT defects including double outlet right ventricle (DORV) and conal ventricular septum defects (VSDs). We found that Gata4 is required within Hedgehog (Hh)-receiving second heart field (SHF) progenitors for normal OFT alignment. Increased Pten-mediated cell-cycle transition, rescued atrial septal defects but not OFT defects in Gata4 heterozygotes. SHF Hh-receiving cells failed to migrate properly into the proximal OFT cushion in Gata4 heterozygote embryos. We find that Hh signaling and Gata4 genetically interact for OFT development. Gata4 and Smo double heterozygotes displayed more severe OFT abnormalities including persistent truncus arteriosus (PTA) whereas restoration of Hedgehog signaling rescued OFT defects in Gata4-mutant mice. In addition, enhanced expression of the Gata6 was observed in the SHF of the Gata4 heterozygotes. These results suggested a SHF regulatory network comprising of Gata4, Gata6 and Hh-signaling for OFT development. This study indicates that Gata4 potentiation of Hh signaling is a general feature of Gata4-mediated cardiac morphogenesis and provides a model for the molecular basis of CHD caused by dominant transcription factor mutations.Author SummaryGata4 is an important protein that controls the development of the heart. Human who possess a single copy of Gata4 mutation display congenital heart defects (CHD), including the double outlet right ventricle (DORV). DORV is an alignment problem in which both the Aorta and Pulmonary Artery originate from the right ventricle, instead of originating from the left and the right ventricles, respectively. To study how Gata4 mutation causes DORV, we used a Gata4 mutant mouse model, which displays DORV. We showed that Gata4 is required in the cardiac precursor cells for the normal alignment of the great arteries. Although Gata4 mutation inhibits the rapid increase in number of the cardiac precursor cells, rescuing this defects does not recover the normal alignment of the great arteries. In addition, there is a movement problem of the cardiac precursor cells when migrating toward the great arteries during development. We further showed that a specific molecular signaling, Hh-signaling, is responsible to the Gata4 action in the cardiac precursor cells. Importantly, over-activating the Hh-signaling rescues the DORV in the Gata4 mutant embryos. This study provides an explanation for the ontogeny of CHD.

scholarly journals HYDATID CYST OF THE INTERVENTRICULAR SEPTUM OF THE HEART WITH RUPTURE INTO THE RIGHT VENTRICLE

1962 ◽  
Vol 44 (1) ◽  
pp. 110-114 ◽  
Author(s):  
Hernán Artucio ◽  
José L. Roglia ◽  
Raúl Di Bello ◽  
Jorge Dubra ◽  
Agustín Gorlero ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Hydatid Cyst ◽  
Interventricular Septum ◽  
The Right

Abstract P457: Systems Analysis To Understand The Impact Of The CDK Module On Cardiomyocyte Proliferation

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Bryana N Harris ◽  
Laura Woo ◽  
Jeffrey J Saucerman
Keyword(s):  
Experimental Data ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Dna Synthesis ◽  
Current Knowledge ◽  
Cycle Phase ◽  
Cyclin D ◽  
Cardiomyocyte Proliferation ◽  
The Core ◽  
The Impact

Rationale: Heart failure is caused by the inability of adult mammalian hearts to overcome the loss of cardiomyocytes (CMs). This is due partly to the limited proliferative capacity of CMs, which exit the cell cycle and do not undergo cell division. Current knowledge in cardiac regeneration lacks an understanding of the molecular regulatory networks that determine whether CMs will progress through the cell cycle to proliferate. Our goal is to use computational modeling to understand the expression and activation levels of the core cell cycle network, specifically cyclins and cyclin-cyclin-dependent kinase (CDK) complexes. Methods: A model of core cell cycle dynamics was curated using previously published studies of CM proliferation regulators. This model incorporates those regulators known to stimulate G1/S and G2/M transitions through the core CDKs. The activity of each of the 22 network nodes (22 reactions) was predicted using a logic-based differential equation approach. The CDK model was then coupled with a minimal ODE model of cell cycle phase distributions and validated based on descriptions and experimental data from the literature. To prioritize key nodes for experimental validation, we performed a sensitivity analysis by stimulating individual knockdown for every node in the network, measuring the fractional activity of all nodes. Results: Our model confirmed that the knockdown of p21 and Rb protein and the overexpression of E2F transcription factor and cyclinD-cdk4 showed an increase in cells going through DNA synthesis and entering mitosis. A combined knockdown of p21 and p27 showed an increase of cells entering mitosis. Cyclin D-cdk4 and p21 overexpression showed a decrease and increase of Rb expression, respectively. Of the 14 model predictions, 12 agreed with experimental data in the literature. A comprehensive knockdown of the model nodes suggests that E2F (a key transcription factor driving DNA synthesis) is positively regulated by cyclin D while negatively regulated by GSK3B, SMAD3, and pRB. Conclusion: This model enables us to predict how cardiomyocytes respond to stimuli in the CDK network and identify potential therapeutic regulators that induce cardiomyocyte proliferation.

Cat heart acetylcholine: structural proof and distribution

1976 ◽  
Vol 231 (3) ◽  
pp. 781-785 ◽  
Author(s):  
OM Brown
Keyword(s):  
Left Ventricle ◽  
Right Ventricle ◽  
Left Atrium ◽  
Right Atrium ◽  
Interventricular Septum ◽  
Pyrolysis Product ◽  
Heart Tissue ◽  
Choline Esters ◽  
The Right ◽  
Cat Heart

The distribution of acetylcholine (ACh) in the cat heart was investigated by a pyrolysis-gas chromatography (PGC) method. The hearts were dissected into various regions and homogenized in acetonitrile in the presence of propionylcholine, internal standard. Following extraction with toluene and hexane, the choline esters were precipitated as the enneaiodide complex. The isolated choline esters were analyzed by PGC, and the peak corresponding to ACh was quantified. The compound extracted from heart tissue that eluted with the retention time of authentic ACh was identified by mass spectrometry as dimethylaminoethylacetate, the pyrolysis product of ACh. ACh concentrations were found to be higher in the atria than the ventricles. In both the atria and the ventricles, a higher content of ACh was found in the right than the left portions: right ventricle, 5.0 compared to left ventricle, 2.0 nmol/g; and right atrium, 16.8 compared to left atrium, 11.3 nmol/g. Some cats were subjected to a bilateral cervical vagotomy 3 wk before removal and analysis of heart tissue. Hearts from vagotomized cats contained less ACh than controls in the right ventricle (-31%), right atrium (-54%), SA node (-42%), and papillary muscle (-53%), but no decreases were found in the left ventricle, left atrium, or interventricular septum.

Defective regional myocardial development and vascularization in one variant of tricuspid atresia—clinical and necropsy findings in three cases

1992 ◽  
Vol 2 (1) ◽  
pp. 42-52 ◽  
Author(s):  
William N. O'Connor ◽  
Carol M. Cottrill ◽  
Michael T. Marion ◽  
Jacqueline A. Noonan
Keyword(s):  
Coronary Artery ◽  
Right Ventricle ◽  
Tricuspid Valve ◽  
Right Coronary Artery ◽  
Interventricular Septum ◽  
Ventricular Myocardium ◽  
Tricuspid Atresia ◽  
Subaortic Stenosis ◽  
Myocardial Development ◽  
The Right

SummaryFive previously reported cases have established the combination of a small right ventricle (sometimes with Uhl's anomaly), imperforate tricuspid valve with fibrotic tensor apparatus, congenital absence of the pulmonary valve, and an intact interventricular septum with muscular subaortic stenosis as a rare variant of tricuspid atresia. In this study of three new autopsy cases, we additionally identified Ebstein's malformation of the imperforate tricuspid valve, partial Uhl's anomaly, regional dysplasia of right ventricular myocardium and thinning of the interventricular septum by intramyocardial sinusoids from the right ventricle. All three new cases had epicardial anomalies of the right coronary artery—a fistula to right ventricle, ostial stenosis and proximal arterial hypoplasia. Sinusoidal connections from the right ventricle to the right coronary artery and to the sclerotic left anterior descending artery were identified in serial sections of the right ventricle and septum. Myofiber disarray, with thick walled intramyocardial arteries and sinusoids from left ventricle, involved the bulging subaortic interventricular septum. These studies are consistent with the hypothesis that defective development of the the right ventricle, along with its blood supply and associated atrioventricular and arterial valves, may underlie this unusual form of congenital heart disease.

Spontaneous regression of a large rhabdomyoma of the interventricular septum

2013 ◽  
Vol 24 (2) ◽  
pp. 379-381 ◽  
Author(s):  
Elena G. Milano ◽  
Maria A. Prioli ◽  
Corrado Vassanelli
Keyword(s):  
Right Ventricle ◽  
Spontaneous Regression ◽  
Interventricular Septum ◽  
In Utero ◽  
Gestation Period ◽  
The Right

AbstractWe report the case of a large congenital rhabdomyoma of the interventricular septum diagnosed prenatally. The foetus was strictly monitored with ultrasound throughout the gestation period showing that the mass had increased in size until delivery. Despite the size of the mass, which appeared to occupy the right ventricle, the baby presented no symptoms both in utero and after birth. Serial echocardiography was used to document the regression of the mass in childhood.

scholarly journals INFLUENCE OF NOCTURNAL INCREASE OF BLOOD PRESSURE ON CARDIAC REMODELING IN PATIENTS WITH ARTERIAL HYPERTENSION

2019 ◽  
Vol 19 (1-2) ◽  
pp. 65-69
Author(s):  
A. I Miroshnichenko ◽  
K. M Ivanov
Keyword(s):  
Blood Pressure ◽  
Left Ventricle ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Antihypertensive Therapy ◽  
Cardiac Remodeling ◽  
Interventricular Septum ◽  
Posterior Wall ◽  
The Right ◽  
Group 1

Actuality. Arterial hypertension (AH) is the main risk factor for the development of cardiovascular diseases, disability and cardiovascular mortality. Episodes of blood pressure (BP) increase during the day in patients receiving antihypertensive therapy are an unfavourable factor contributing to the development and progression of cardiac remodeling. Aim. The purpose of the research is to study the features of changes in the structural and functional state of the heart under the influence of high blood pressure at night in patients with arterial hypertension with the dynamic three-year observation. Material and methods. 47 patients with the diagnosis of AH were examined. Patients were divided into two groups, randomized by age, duration and severity of AH. Group 1 included 24 patients who as a result of ambulatory blood pressure monitoring (ABPM) on the background of combined antihypertensive therapy suffered from constantly increased BP at night. The second group combined 23 patients without the increase in BP during the night according to the ABPM with antihypertensive therapy. The examination included measurement of the office BP, ABPM, two-fold echocardiography with a three-year interval. Results. When assessing the indices of office BP in the groups, there were no significant differences, all patients achieved the target values of BP. In patients in Group 1, higher values of BP were observed during the day, according to ABPM. Echocardiography over a three year period of observation revealed a more pronounced increase in diastolic interventricular septum thickness, the thickness of the left ventricle posterior wall during diastole, sizes of left atrium in the patients of the first group, patients of the second group had a more pronounced thickness of the left ventricle posterior wall during systole. The increase in the size of the right ventricle was revealed in both groups. Conclusions. 1) In patients with the increase in blood pressure at night, the values of BP variability were higher during the day. 2) Three-year dynamic observation revealed that the increase in BP at night in patients with hypertension facilitated acceleration of cardiac remodelling and was associated with an increase in the left ventricular posterior wall, interventricular septum thickness, the size of the left atrium, and the size of the right ventricle.

scholarly journals Echocardiographic and Doppler Aspects of Chronic Pulmonary Heart. About 11 cases

2021 ◽  
Vol 04 (16) ◽  
pp. 01-07
Author(s):  
Bani Am
Keyword(s):  
Right Ventricle ◽  
Inferior Vena ◽  
Interventricular Septum ◽  
Vena Cava ◽  
Maximum Velocity ◽  
Heart Patients ◽  
Specificity And Sensitivity ◽  
Chest X Ray ◽  
The Mean ◽  
The Right

Pulmonary chronic heart (CPC) is an enlargement associated or not with dilation of the right ventricle. Objective: To recall the echocardiographic-Doppler aspects essential for the screening of pulmonary chronic heart. Patients and method: Retrospective study carried out between January 2009 and April 2019 interesting the cases of pulmonary chronic heart. Results: out of 124 cases of pulmonary chronic heart, 11 cases were included. These were four men and 7 women with a mean age of 63 ± 19 years (range: 20-84 years). The radiological and electrical semiology of pulmonary chronic heart was found, lacking specificity and sensitivity. Dilation of the right heart chambers, dyskinesia of the interventricular septum and hypertrophy of the free wall of the right ventricle ˃ 5 mm were observed. The mean maximum velocity of tricuspid insufficiency on continuous Doppler was 4.6 ± 1.32 ms / s (Extremes: 3.59-7.58 m / s) and the mean dilation of the inferior vena cava was 23.2 ± 3.9mm (Extreme: 21.2-27mm). Conclusion: CPC is uncommon and predominant in women. The EKG and chest X-ray are first-line exams without sensitivity or specificity. Screening for CPC is based on echocardiographic-Doppler criteria. The right cardiac catheterization remains the key examination.

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