Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Heart development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMed2001

TGFbeta Type III and TGFbeta Type II receptors have distinct activities during epithelial-mesenchymal cell transformation in the embryonic heart.

During the early stages of heart development, progenitors for the heart valves and septa come from endothelial cells via a developmental process known as "epithelial-mesenchymal cell transformation." This process is restricted to the atrioventricular (AV) canal and outflow tract portions of the embryonic heart. TGFbeta signal transduction pathways play critical roles during epithelial-mesenchymal cell transformation in heart development. Previously, we showed that both TGFbeta Type II (TbetaRII) and Type III (TbetaRIII) receptors are required to mediate epithelial mesenchymal cell transformation in chick heart. Further, distinct TGFbeta2 and TGFbeta3 activities correspond to separate components of the embryonic cell transformation process. Studies by others of TGFbeta-mediated inhibition of cell proliferation produced a model where TbetaRIII functions by facilitating TGFbeta2 binding to TbetaRII. In the present study, we provide evidence that TbetaRIII mediates distinct cellular responses from those of TbetaRII. Blocking antibody for TbetaRIII, but not antibody against TbetaRII, specifically inhibits the endothelial cell-cell separation step. Examination of developmental markers, perturbed by blocking TbetaRIII antibody, revealed a pattern of expression distinctively different from that of TbetaRII antibody treatment. These data show that a distinct TbetaRIII-mediated process is required for endothelial cell-cell separation during epithelial mesenchymal cell transformation. As TGFbeta2 mediates endothelial cell-cell separation, the data point to a specific association of TGFbeta2 and TbetaRIII in the cell separation step of epithelial mesenchymal cell transformation. We conclude that distinct TbetaRII and TbetaRIII signal transduction pathways mediate epithelial-mesenchymal cell transformation in the heart.

Animals↗
PubMed2004

Approach to Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy is a genetic disease characterized by marked left ventricular (LV) hypertrophy. A dynamic LV outflow obstruction is present in approximately 20% of patients. Many affected individuals remain asymptomatic throughout life, others develop heart failure symptoms or atrial fibrillation (AF), and some die suddenly, often young and in the absence of previous symptoms. Stratification of sudden death risk is based on several markers, including a previous cardiac arrest, sustained ventricular tachycardia, family history of sudden death, extreme LV hypertrophy (>/= 30 mm), syncope, nonsustained ventricular tachycardia on Holter, and abnormal exercise blood pressure response. The implantable cardioverter-defibrillator is the most effective treatment for sudden death prevention, and should be considered in patients with either one strong or multiple risk factors. Important symptoms of heart failure develop in a minority of patients, largely as a consequence of diastolic dysfunction, and are usually treated with beta blockers, or verapamil. In patients with LV obstruction and severe symptoms unresponsive to medications, myectomy operation or alcohol septal ablation is indicated for relieving the gradient and improving quality of life. AF develops in approximately 20% of patients. Amiodarone is the most effective medication for preventing AF recurrences. In chronic AF, beta blockers or verapamil are usually effective for heart rate control. The threshold for anticoagulants is low, because even brief AF episodes have a substantial embolization risk.

Journal Article↗
PubMed1994

Transcriptional regulation of lipoprotein lipase in the heart during development in the rat.

Lipoprotein lipase (LPL) is differentially expressed in fat and heart under a variety of physiological conditions, particularly during development. LPL activity, protein and mRNA levels have been shown to rise dramatically during the first three weeks of life. The mechanism responsible for these changes in LPL in the heart during development are not fully understood. In order to address the changes in LPL in the heart during development, we measured steady state levels of LPL mRNA and the rate of LPL transcription during development. Northern blot analysis of LPL mRNA in the heart of rats from 5-120 days of age showed no changes in transcript size; however, steady state levels of LPL mRNA increased approximately 10-fold by day 20 and remained elevated thereafter. The rate of LPL transcription increased dramatically between day 5-20 and remained elevated thereafter. Thus, as opposed to other settings where posttranscriptional and posttranslational mechanisms can be important, the increased expression of LPL in rat heart that occurs during development appears to be largely due to the transcriptional activation of the gene.

Animals↗
PubMed1985

Effect of strontium on the contractile properties of postnatally developing rat heart ventricles.

The effects of substitution of calcium (Ca) by an equimolar concentration of strontium (Sr) on isometric contractions of isolated ventricular muscle from postnatally developing rat heart were studied. The duration of contraction and the time-to-peak tension were increased in all age groups although much less in the adult rats than in the neonates. The contractile force was increased in the muscles of rats between 1 and 14 days of age but was depressed in the older animals. The prominent rest-twitch potentiation of neonatal rat heart in Ca-Tyrode was totally eliminated by Sr, whereas a clear rest-twitch potentiation was induced by this cation in the adult rat heart, in which tissue the potentiation is normally absent in Ca-Tyrode. The maximal twitch potentiation by rest in Ca-Tyrode and the positive inotropic effect of Sr substitution grew from birth up to day 9 and from then gradually declined towards the level of adult rat heart by the end of the 3rd postnatal week. The phase of increasing rest-twitch potentiation coincides fairly well with the known development of sarcoplasmic reticulum and the phase of decline with the appearance of the T system of the sarcolemma. It is suggested that the qualitative changes in the contractile properties of developing rat heart during the 3rd postnatal week are due to the more efficient utilization of intracellular calcium stores, owing to the development of the T system.

Animals↗
PubMed1997

Caffeine-induced contractions in developing rabbit heart.

Mature myocardium utilizes calcium released by the sarcoplasmic reticulum (SR) for cell contraction. Transient exposure of mature myocytes to caffeine is known to directly trigger Ca2+ release from the SR. In contrast, neonatal rabbit heart cells rely on transsarcolemmal Ca2+ influx for tension generation. SR function is decreased in immature heart and appears to play a minimal role as a calcium source. Accordingly, we hypothesized that neonatal rabbit myocytes would not respond to a caffeine pulse. Isolated neonatal and adult myocytes were paced to load the SR with calcium and then exposed to a 1-s pulse of 10 mM caffeine. As previously described, adult myocytes exhibited a brisk contraction in response to caffeine. Unexpectedly, neonatal myocytes also exhibited a similar, brisk response. These caffeine-induced contractions were not dependent on extracellular Ca2+ but were dependent upon the loading of SR Ca2+ stores. When SR Ca2+ stores were depleted by exposure to caffeine, mature myocytes exhibited only small, slow contractions in response to electrical field stimulation. Replenishing the SR Ca2+ stores resulted in normal, brisk contractions. In contrast, electrically stimulated contractions in immature myocytes were largely unaffected by caffeine-induced SR depletion. Thus, although neonatal myocytes are capable of loading and releasing calcium from the SR, such SR calcium release is not normally required for contraction in the developing heart. The minor role of SR Ca2+ release in immature rabbit heart may not result from immaturity of the SR, but rather from an inadequate mechanism to trigger SR calcium release.

Animals↗
PubMed2002

alpha 1 Connexin (connexin43) gap junctions and activities of cAMP-dependent protein kinase and protein kinase C in developing mouse heart.

alpha 1 Connexin (connexin43) is the dominant gap junction protein of the developing and mature heart where it forms channels that mediate intercellular electrical and metabolic coupling events that are critical for heart function. alpha1 connexin channels are rapidly and reversibly gated by actions of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC), and disruption of consensus sites for these phosphorylations are associated with severe heart malformations. However, there have been no reports on the relative activities of PKA or PKC in early heart formation. Nor has the presence and phosphorylation state of alpha1 connexin been documented in these same developmental stages. To begin these studies, we used hearts from 8.5-18.5 dpc (days postcoitus) mouse embryos, postpartum pups, and adults. Membrane or supernatant fractions were used for immunoblots to assess the amounts and distribution of alpha1 connexin protein and each protein kinase. Phosphotransferase assays were done to document the endogenous activities of PKA and PKC. Three species of alpha1 connexin at 44, 46, and 49 kDa were evident in 8.5- and 9.5-dpc embryos and adult hearts, but the 49-kDa band was not consistently found in 10.5 dpc or embryos through 18.5 dpc, although it was robust in adult heart. The amount of PKA was minimal in 8.5-dpc hearts but rose thereafter and was maximal by 10.5 dpc and remained stable throughout development. Catalytic activity of this enzyme was minimal in 8.5-dpc hearts then rose thereafter and was maximal by 10.5 dpc of development. PKC delta was confined mainly to membrane fractions, whereas PKC epsilon had supernatant- and membrane-associated forms. Both enzyme isoforms showed large fluctuations throughout development. In 8.5- and 9.5-dpc hearts, PKC catalytic activity was maximal but, by 10.5 dpc, activity dramatically declined and remained low thereafter. The results demonstrate that alpha1 connexin is present at the heart tube stage (8.5 dpc) of development onward and provide evidence suggesting that channels formed by this protein are dynamically regulated by PKA and PKC, especially in 8.5- and 9.5-day embryonic hearts, which are crucial times for heart formation and left/right patterning in general.

Animals↗
PubMed1996

Effect of long-term treatment with selective vasopressin V1 and V2 receptor antagonist on the development of heart failure in rats.

Vasopressin has been implicated in the pathogenesis of heart failure as one of the most potent vasoconstrictors. However, whether the increase in plasma vasopressin levels modifies the pathophysiology of heart failure remains unknown. To investigate the effect of long-term inhibition of vasopressin in the development of heart failure, we administered a selective, orally effective, nonpeptide vasopressin antagonist, the V1 receptor antagonist OPC-21268 (100 mg center dot kg-1 center dot day-1) or a V2 receptor antagonist, OPC-31260 (20 mg center dot kg-1 center dot day-1) to rats with heart failure induced by the creation of an aortocaval fistula (AVF) and to sham-operated rats for 4 weeks, beginning on the first postoperative day. The heart failure in this experiment was characterized by an increase in the weights of the right and left ventricles, the lungs, and the right and left appendage, increase in left ventricular end-diastolic pressure (LVEDP), increase in right ventricular systolic pressure (RVSP), increase in right atrial pressure (RAP), and an increase in the plasma level of atrial natriuretic peptide (ANP) as compared with no change in sham-operated rats. There were no differences in shunt ratio between treated and untreated heart failure groups. Chronic administration of the V2 receptor antagonist OPC-31260 significantly reduced the weight of the right ventricle (1.17 +/- 0.39 vs. 0.90 +/- 0.13 g/kg, p < 0.05), RVSP (53 +/- 18 vs. 39 +/- 4 mm Hg, p < 0.05), LVEDP (11.8 +/- 5.2 vs. 6.5 +/- 2.8 mm Hg, p < 0.05) and the plasma concentrations of ANP (554 +/- 271 vs. 193 +/- 39 pg/ml, p < 0.05) as compared with the values of rats with untreated HF. Chronic treatment with the V1 receptor antagonist OPC-21268 did not alter hemodynamics, organ weights, or hormone concentrations. These results suggest that vasopressin did not contribute mainly to the maintenance of systemic hemodynamics through the V1 receptor in this heart failure model. Vasopressin may play a role, at least in part, in the fluid retention in the development of heart failure through the V2 receptor. OPC-31260 may present a new approach to the treatment of heart failure.

Animals↗
PubMed1990

Distribution of vitronectin in the embryonic chick heart during endocardial cell migration.

In the early phase of heart development, the endocardial cells migrate into the truncal swellings and atrioventricular (AV) cushions, and become mesenchymal cells. Vitronectin is a glycoprotein which is thought to mediate cell migration. The present study demonstrates by immunohistochemistry the distribution of vitronectin in order to elucidate its contribution to endocardial cell migration in the developing chick heart. At Hamburger and Mamilton's stage 23, the network of fibrillar material filled the extracellular space of both truncal swellings and AV cushions. The fibrillar network has been thought to be a matrix for endocardial cell migration. The network was stained with the anti-vitronectin antibody. At stage 29, the swellings and cushions were packed with mesenchymal cells, though immunoreactivity to the antibody was still observed in the extracellular matrix. The myocardium facing the AV cushions reacted to the antibody, but the myocardium surrounding the truncus arteriosus did not. The intensity of the immunohistochemical staining of the myocardium facing the AV cushions increased and reached a peak at stages 24 to 26, and then became weak by stage 29. The endocardial sheet, aortico-pulmonary septum and developing tunica media of the great arteries were not stained by the antibody at any stage. These results strongly suggest that vitronectin is involved in the migration of endocardial cells, and that the myocardium facing the AV cushions produces vitronectin.

Animals↗
PubMed1995

Section directed cryosectioning of specimens for scanning electron microscopy: a new method to study cardiac development.

A new method to study the developing heart was developed. Using this "section directed" cryosectioning method, appropriate fixed embryos can be trimmed optimally to obtain sectional planes that, if necessary, can be matched with histologically treated sections. As a result, the morphological information obtained with the scanning electron microscope can be compared in detail with the information on the molecular phenotypes of the subpopulations of cells as deducted from staining patterns of the sections. This method allows combination of the specific advantages of sophisticated histological techniques, such as immunohistochemistry and in situ hybridisation, with those of the scanning electron microscope.

Animals↗
PubMedDate not supplied

Abnormal expression of genes associated with development and inflammation in the heart of mouse maternal phenylketonuria offspring.

This study describes gene expression in the fetus hearts obtained from mouse model for phenylketonuria. These hearts have cardiovascular disease (CVD). Therefore genes involved in CVD were examined. Several genes associated with heart development and inflammation were found to be altered. In order to investigate whether the abnormal gene expression alters transcription and translation, the levels of troponin mRNA and protein were determined. One step real time RT-PCR showed a reduction in cardiac troponin I, troponin T2 and ryanodine receptor 2. Determination of troponin I and T protein levels showed reduced levels of these proteins. Our results suggest that altered gene expression affects protein production. These changes are likely involved in the cardiovascular defects seen in the mouse.

Animals↗
PubMed1989

[Development of the avian and mammalian heart prior to the onset of blood circulation, studied in chick and mouse embryos].

Heart development, its morphological and functional development prior the start of blood circulation were compared in chicken and mouse embryos. At beginning of neurula stage, when also somites appear, the cardiogenic mesoderm forms into tissue of epithelial type and cardiac plate is developed in wall of pleuroperitoneal cavity. In conjugated cardiac plate, primordial cardiac cavity fundaments appear in the about 30-hour old chicken embryo with 6-7 somites. First myoblasts (and spontaneous action potentials) can be observed in the ventricular part of embryos with 7 somites. Hence, muscular differentiation is expanded to atrial section. In embryo with 9-10 somites straight cardiac tube is developed, its ventricular section pulsates feebly, but it is unable for blood circulation yet. Pacemaker tissue of cardiac tube is in the atrium. At the end of second day the first curvature of heart appears and myocytes of venous sinus become pacemaker. At the end of neurula stage the blood circulation starts in two-day old embryo with 16 somites. Development of heart of mammalian embryos differs in several aspects from cardiac development of avian ambryos. In mammals transformation and differentiation of cells in cardiac plate and primordial cardiac fundaments have a cranio-caudal trend and in nearly same developmental stage as in chicken. In mouse circulation is started by curved cardiac tube of embryo with 10-12 somites (eight and half day old) at the end of neurala stage.

Animals↗
PubMed2006

Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis.

OBJECTIVES: To analyze the potential contribution of contractility state and ventricular geometry to the development of heart failure in rats with aortic stenosis. METHODS: Rats were divided into three groups: compensated aortic stenosis (AS, n=11), heart failure AS (n=12) and control rats (C, n=13). RESULTS: After 21 weeks, failing AS rats presented higher systolic (C=36.6+/-3.1, AS=78.6+/-4.8*, failing AS=104.6+/-7.8*(dagger)) and diastolic meridian stress (C=6.9+/-0.4, AS=20.1+/-1.1*, failing AS=43.2+/-3.2*(dagger)), hydroxyproline (C=3.6+/-0.7 mg/g, AS=6.6+/-0.6* mg/g, failing AS=9.2+/-1.4*(dagger) mg/g) and cross-sectional area (C=338+/-25 microm2, AS=451+/-32* microm2, failing AS=508+/-36*(dagger) microm2), in comparison with control and compensated AS animals (*p<0.05 vs. control, (dagger)p<0.05 vs. AS). In the isometric contraction study, considering the time from peak tension to 50% relaxation (RT50), the relative variation responses, following post-rest contraction and increase in Ca2+ concentration, were higher in failing AS than compensated AS animals. In contrast, following post-rest contraction, compensated AS group presented higher values of the peak developed tension (DT) than failing AS group. Following beta-adrenergic stimulation, control animals presented higher values of +dT/dt and -dT/dt than AS animals. In addition, failing AS animals presented higher TPT values than compensated AS animals. CONCLUSION: Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis.

Animals↗
PubMed2001

Depression and risk of heart failure among older persons with isolated systolic hypertension.

BACKGROUND: Investigators have shown that depression is associated with an increased risk of coronary heart disease in general and myocardial infarction in particular. However, it is unknown whether depression, independent of its association with myocardial infarction, is a risk factor for heart failure. METHODS: This study examined whether depression was a predictor of incident heart failure among 4538 persons aged 60 years and older with isolated systolic hypertension who were enrolled in the Systolic Hypertension in the Elderly Program (SHEP). Depression was defined as a score of 16 or more at baseline on the Center for Epidemiological Studies Depression Scale (CES-D). The relationship between depression and heart failure was assessed using Cox proportional hazards regression. RESULTS: The average follow-up was 4.5 years. Heart failure developed in 138 (3.2%) of 4317 nondepressed persons and in 18 (8.1%) of 221 depressed persons. After controlling for age; sex; race; history of myocardial infarction, diabetes, or angina; blood pressure; cholesterol levels; electrocardiographic abnormalities; smoking; disability; and SHEP treatment group, depressed persons had more than a 2-fold higher risk of developing heart failure compared with nondepressed persons (hazard ratio, 2.59; 95% confidence interval, 1.57-4.27; P<.001). After additional adjustment for the occurrence of myocardial infarction during follow-up, depressed persons remained at elevated risk of heart failure (hazard ratio, 2.82; 95% confidence interval, 1.71-4.67; P<.001). CONCLUSIONS: Depression is independently associated with a substantial increase in the risk of heart failure among older persons with isolated systolic hypertension. This association does not appear to be mediated by myocardial infarction.

Aged↗
PubMed2004

Molecular cytogenetic characterization of ring chromosome 15 in three unrelated patients.

We report molecular cytogenetic characterization of ring chromosome 15 in three unrelated male patients with the karyotype 46,XY,r(15). One was a stillborn child with several malformations, and the other two cases showed pre- and postnatal growth retardation and developmental delay, common features for ring chromosome 15 syndrome. One of these patients also displayed clinical features resembling Prader-Willi syndrome (PWS). To delineate the extent of the deletion on chromosome 15, we have carried out fluorescence in situ hybridization (FISH) using bacterial artificial chromosomes (BACs) mapping to the distal long arm of chromosome 15. The deletion breakpoints clustered within a 4.5-6.5 Mb region proximal to the 15q telomere. Two deletions involved the same known genes, while the largest deletion observed in the stillborn child involved three additional genes, including the COUP-TFII gene, which has been suggested to play a role in heart development. The heart malformations, which are observed in this patient, are thus likely to be due to hemizygosity/haploinsufficiency of the COUP-TFII gene. In all three patients, the insulin-like growth factor I receptor gene (IGF1R) gene was deleted supporting the association between IGF1R and growth retardation seen in ring chromosome 15 syndrome.

Abnormalities, Multiple↗
PubMed2004

Hypoglycemia induced changes in cell death and cell proliferation in the organogenesis stage embryonic mouse heart.

BACKGROUND: Hypoglycemia is a side effect of diabetes therapy and causes abnormal heart development. Embryonic heart cells are largely resistant to teratogen-induced apoptosis. METHODS: Hypoglycemia was tested for effects on cell death and cell proliferation in embryonic heart cells by exposing mouse embryos on embryonic day (E) 9.5 (plug = E0.5) to hypoglycemia (30-50 mg/dl glucose) in vivo or in vitro for 24 hr. Long-term effects of in vivo exposure on conceptus viability were evaluated at E18.5. Cell death was evaluated on E10.5 by: 1) two TUNEL assays in sectioned embryos to demonstrate DNA fragmentation; 2) confocal microscopy in whole embryos stained with Lysotracker; 3) flow cytometry in dispersed heart cells stained for TUNEL and myosin heavy chain (MHC) to quantify and characterize cell type susceptibility; and 4) immunohistochemistry (IHC) and Western analysis in sectioned embryos to evaluate potential involvement of caspase-3 active subunit and p53. Effects on cell proliferation were evaluated by IHC and Western analysis of proliferating cell nuclear antigen (PCNA). RESULTS: In vivo hypoglycemic exposure on E9.5 reduced viability in conceptuses examined on E18.5. Hearts examined on E10.5 demonstrated increased TUNEL and Lysotracker staining. In hearts of embryos exposed to hypoglycemia, flow cytometry demonstrated increased TUNEL-positive cells and cells dual-labeled for TUNEL and MHC. Protein expression of caspase-3 active subunit and p53 was increased and PCNA was markedly reduced in hearts of embryos exposed to hypoglycemia. CONCLUSIONS: Hypoglycemia reduces embryonic viability, induces significant cell death, and reduces cell proliferation in the E9.5 mouse heart, and these processes may involve active caspase-3 and p53.

Animals↗
PubMed1976

Morphological and biochemical abnormalities in hearts of cardiac mutant salamanders (Ambystoma mexicanum).

The effect of homozygosity for recessive gene c in Ambystoma mexicanum is the absence of a heartbeat even though initially heart development appears normal. Mutant embryos (c/c) are first distinguishable from their normal siblings (+/+;+/c) at stage 34 (7 days after fertilization) when the normals develop contracting hearts. The mutant hearts at this stage, upon gross examination, appear structurally normal but fail to beat. Nevertheless, the mutants survive through stage 41, which is about 20 days beyond the heartbeat stage, and they exhibit normal swimming movements, indicating that gene c does not affect skeletal muscle. Electron microscopic studies of normal hearts show some myofibrils to be present at stage 34; by stage 41, the normal myocardial cells have become highly differentiated muscle cells. Although some mutant heart cells contain a few thin 60 A and thick 150 A filaments, organized myofibrils are absent. Instead, amorphous proteinaceous collections are prominent. Heavy meromyosin (HMM) binding experiments were performed on mutant hearts to determine whether the myocardial cells contain actin. Mutant myocardial cells that are glycerinated but not treated with HMM contain intact amorphous bodies. After incubation in HMM, the amorphous collections are no longer present and large numbers of decorated actin filaments appear. The.results suggest that the amorphous proteinaceous collections contain actin in a nonfilamentous form, and the addition of HMM induces this actin to polymerize into filaments. SDS-polyacrylamide gel electrophoresis of mutant heart tissue supports this conclusion by showing a prominent 43,000 dalton band suggestive of actin. The electrophoresis experiments also demonstrate a significant reduction of myosin heavy chain (200,000 daltons) in mutant hearts when compared to normal, and this latter observation is confirmed by radioimmunoassay experiments. Muscle tropomyosin (34,000 daltons), prominent in normal hearts, is virtually nonexistent in mutants. Thus, it appears that this single gene mutation affects the accumulation and organization of several different muscle proteins, including actin, myosin, and tropomyosin.

Actins↗
PubMed1998

Altered apoptosis levels in hearts of human fetuses with Down syndrome.

OBJECTIVE: We sought to test the hypothesis that apoptosis is a method of remodeling in second-trimester fetal heart development. We also hypothesized that hearts from fetuses with Down syndrome would have different levels of apoptosis than would control hearts, associated with their abnormal heart development. STUDY DESIGN: We obtained hearts from fetuses between 14 and 23 weeks' gestation with Down syndrome without anomalies (n = 10) and with the atrioventricular canal defect (n = 5). These hearts were compared with control hearts without anomalies (n = 5). Hearts were subjected to in situ end-labeling of deoxyribonucleic acid to test for evidence of apoptosis. The apoptotic indices were compared by anatomic location. RESULTS: Apoptotic nuclei were observed in each anatomic location in every category. The apoptotic indices were significantly lower in the atrial myocardial tissues of fetuses with Down syndrome than in control preparations (P < .05). The apoptotic index did not differ significantly in the atrial septum, ventricular myocardium, or ventricular septum. CONCLUSIONS: Apoptosis occurs in human fetal hearts during the second trimester. The different levels observed in our study suggest a different remodeling process in hearts of fetuses with Down syndrome than in hearts of control fetuses. Further study is needed to determine whether the different level of apoptosis associated with Down syndrome is due to the abnormal karyotype or to the presence of an anomaly.

Apoptosis↗
PubMed2005

Jumonji regulates cardiomyocyte proliferation via interaction with retinoblastoma protein.

Jumonji (JMJ) can function as a transcriptional repressor and plays critical roles in embryonic development including heart development in mice. Although JMJ has been suggested to play a role in cell growth, the molecular mechanisms have not been resolved. The present data demonstrate that JMJ interacts with the retinoblastoma protein (Rb), one of the master regulatory genes of cell cycle. JMJ potentiates the repression function of Rb on E2F activities, leading to reduced cell cycle progression. The transcriptional repression domain of JMJ is critical for the interaction with Rb as well as repression of cell cycle. The physiological relevance of the association between Rb and JMJ was assessed in cardiomyocytes. Primary cardiomyocytes cultured from homozygous jmj knock-out mouse embryos (jmj mutants) show increased cell mitosis in a cardiomyocyte-specific manner. Reporter gene analyses demonstrate that promoter activities of cyclin D1, cyclin D2, and Cdc2 are up-regulated in jmj mutant cardiomyocytes. These data suggest that JMJ down-regulates the cell growth via interaction with Rb, which would provide important insights into the cardiac defects observed in jmj mutant mice.

Animals↗