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PubMed2000

Gene dosage affects the cardiac and brain phenotype in nonmuscle myosin II-B-depleted mice.

Complete ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice resulted in cardiac and brain defects that were lethal during embryonic development or on the day of birth. In this paper, we report on the generation of mice with decreased amounts of NMHC-B. First, we generated B(DeltaI)/B(DeltaI) mice by replacing a neural-specific alternative exon with the PGK-Neo cassette. This resulted in decreased amounts of NMHC-B in all tissues, including a decrease of 88% in the heart and 65% in the brain compared with B(+)/B(+) tissues. B(DeltaI)/B(DeltaI) mice developed cardiac myocyte hypertrophy between 7 months and 11 months of age, at which time they reexpressed the cardiac beta-MHC. Serial sections of B(DeltaI)/B(DeltaI) brains showed abnormalities in neural cell migration and adhesion in the ventricular wall. Crossing B(DeltaI)/B(DeltaI) with B(+)/B(-) mice generated B(DeltaI)/B(-) mice, which showed a further decrease of approximately 55% in NMHC-B in the heart and brain compared with B(DeltaI)/B(DeltaI) mice. Five of 8 B(DeltaI)/B(-) mice were born with a membranous ventricular septal defect. Moreover, 5 of 5 B(DeltaI)/B(-) mice developed myocyte hypertrophy by 1 month; B(DeltaI)/B(-) mice also reexpressed the cardiac beta-MHC. More than 60% of B(DeltaI)/B(-) mice developed overt hydrocephalus and showed more severe defects in neural cell migration and adhesion than did B(DeltaI)/B(DeltaI) mice. These data on B(DeltaI)/B(DeltaI) and B(DeltaI)/B(-) mice demonstrate a gene dosage effect of the amount of NMHC-B on the severity and time of onset of the defects in the heart and brain.

Animals↗
PubMed2003

Insulin regulation in AhR-null mice: embryonic cardiac enlargement, neonatal macrosomia, and altered insulin regulation and response in pregnant and aging AhR-null females.

The aryl hydrocarbon receptor (AhR) was originally characterized because of its high affinity binding of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. However, studies using AhR-null mice have demonstrated the importance of this protein in normal physiology and development. Here we demonstrate that AhR-null embryos develop cardiac enlargement, and that this phenotype is dependent, at least in part, on the maternal genotype. Neonates born to AhR-null females had increased heart weights regardless of the neonatal genotype, an outcome also observed in gestational diabetes. The cardiac hypertrophy markers, beta-myosin heavy chain and atrial natriuretic factor, and the cardiac proliferative index were increased in AhR-null embryos, indicating that the cardiac enlargement is associated with myocyte hypertrophy and hyperplasia, which begin prior to birth. Importantly, two- to three-month-old pregnant and seven-month-old nonpregnant females, but not nonpregnant three-month-old AhR-null females had significantly decreased fasting plasma insulin levels and a reduced ability to respond to exogenous insulin compared to controls. Despite these alterations in insulin regulation and responsiveness, pregnant AhR females did not have abnormal glucose tolerance tests and did not develop hyperglycemia, classic characteristics of gestational diabetes. However, twenty-three percent of seven-month-old AhR-null females did have altered glucose tolerance tests, but did not show hyperglycemia or increased hemoglobin A1C concentration under normal feeding conditions. While the ultimate cause of the neonatal phenotype remains unclear, these studies establish that the AhR is required for normal insulin regulation in pregnant and older mice and for cardiac development in embryonic mice.

Age Factors↗
PubMed1989

[Late episodic hypoxemia and variation in heart rate following major abdominal surgery].

In thirteen patients who were submitted to elective major abdominal surgery, the heart rate and arterial oxygen saturation were monitored continuously on the preoperative night-to-day prior to operation and the first and second postoperative nights (from 11 pm till 7.30 am). The heart rate increased by an average of approximately 22 beats/minute (p less than 0.005) and the oxygen saturation decreased approximately 4.5% (median) (p less than 0.003) after the operation. During the second postoperative night, two patients had 120 and 372 episodes respectively of sudden decrease in saturation to less than 80%. On the morning of the third day, the second of these patients developed cardiac arrhythmia requiring treatment. In one of these patients, the episodes were closely correlated with increase in the heart rate. No connection was observed between administration of opiates and disturbances in oxygen saturation or heart rate. The clinical relevance of episodic decrease in saturation in the late postoperative phase is still unknown but may be of significance for the development of cardiac and cerebral dysfunctions.

Abdomen↗
PubMed1999

ECG abnormalities in tricyclic antidepressant ingestion.

The tricyclic antidepressant (TCA) agents are recognized for their potentially lethal cardiovascular and neurological effects in poisoned patients. The 12-lead electrocardiogram (ECG) has emerged as a popular bedside tool in the evaluation of TCA toxicity. Although the history and physical examination play a key role in the assessment of the patient with potential TCA poisoning, the presence or absence of features of the TCA toxidrome are not sufficient to detect or exclude toxicity from this class of drugs. A variety of ECG findings occur with TCA toxicity. Aside from the sinus tachycardia due principally to anticholinergic effects, TCA-toxic changes seen on the ECG are attributable primarily to the sodium channel blockade caused by these agents. The majority of patients at significant risk for developing cardiac or neurological toxicity will have a QRS complex greater than 0.10 seconds or a rightward shift of the terminal 40 ms of the frontal plane QRS complex vector. The majority of these patients will also display these changes early in their emergency department stay. However, the appearance of these findings, either alone or in combination, does not mean the patient will develop significant cardiac or neurological toxicity. The ECG can neither unequivocally rule in nor rule out impending toxicity; recognizing these limitations, the emergency physician can use this bedside tool in combination with other clinical data during the assessment of the poisoned patient.

Adolescent↗
PubMed1986

Neurogenic antinatriuresis during development of acute cardiac tamponade.

Renal function was measured during the development of cardiac tamponade in anesthetized dogs. Tamponade was induced by infusion of isotonic saline (37 degrees C) into the pericardial space. Step increases in pericardial fluid volume in 20-ml increments from 0 to 160 ml increased renal efferent nerve activity by a total of 140 +/- 58% of control (from 205 +/- 70 microV/s). Since renal nerve traffic was elevated by pericardial fluid volume infusion prior to any changes in arterial pressure, renal function was determined before and after increasing pericardial pressure (PCP) by approximately 5 and 10 mmHg. Increasing PCP by 5 mmHg decreased urinary sodium excretion and increased renin secretion rate without changing mean arterial pressure, renal blood flow, or glomerular filtration rate (GFR). Further elevation of PCP to approximately 10 mmHg also decreased urinary sodium excretion as well as arterial pressure and GFR. Renal denervation prevented both of these antinatriuretic responses to elevated PCP. In a third group of dogs, similar antinatriuresis was induced by increasing PCP by approximately 5 and 10 mmHg. Bilateral cervical vagotomy abolished the antinatriuretic response to increased PCP by 5 mmHg but was ineffective when PCP was increased by 10 mmHg, which was accompanied by decreased arterial pressure. These results demonstrate that elevation of pericardial fluid volume, and consequently PCP, reflexly decreases urinary sodium excretion via activation of renal sympathetic outflow. Early reflex antinatriuresis results primarily from activation of cardiopulmonary or splanchnic receptors with vagal afferents, whereas, at larger PCP, reflex antinatriuresis may result from hypotension and unloading of high pressure baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Glycogen synthase kinase-3beta: a novel regulator of cardiac hypertrophy and development.

Glycogen synthase kinase-3beta (GSK-3beta) is a ubiquitously expressed constitutively active serine/threonine kinase that phosphorylates cellular substrates and thereby regulates a wide variety of cellular functions, including development, metabolism, gene transcription, protein translation, cytoskeletal organization, cell cycle regulation, and apoptosis. The activity of GSK-3beta is negatively regulated by protein kinase B/Akt and by the Wnt signaling pathway. Increasing lines of evidence show that GSK-3beta is an essential negative regulator of cardiac hypertrophy and that the inhibition of GSK-3beta by hypertrophic stimuli is an important mechanism contributing to the development of cardiac hypertrophy. GSK-3beta also plays an important role in regulating cardiac development. In this review, the role of GSK-3beta in cardiac hypertrophy and development and the potential underlying mechanisms are discussed.

Animals↗
PubMed2004

Expression of bone morphogenetic protein-10 mRNA during chicken heart development.

In this communication we describe the expression pattern of BMP10 mRNA during cardiac development in chickens. BMP10 is considered an important factor in the regulation of cardiac growth and trabeculation in the murine embryo. We identified chicken Ests, which are similar to mouse and human BMP10 in the UMIST database. The cDNA clone that contained most sequences was obtained, verified by sequence analysis, and used to determine the spatiotemporal pattern of gene expression. BMP10 mRNA is initially expressed at HH10 in the myocardium of the arterial pole of the heart tube, anterior to the interventricular groove. Between HH14 and HH22, BMP10 mRNA becomes broadly expressed in the outflow tract, the distal part of the inflow tract, and the trabeculated part of the developing ventricles and atria. From HH31 onward, BMP10 mRNA expression decreases in the ventricular myocardium by first disappearing from the compact myocardium and then from the tips of the trabecules. At HH44, BMP10 mRNA is expressed only in the trabeculated myocardium of the atria and the endocardium of the ventricles. The observed expression pattern of BMP10 mRNA suggests that it may play a role in regulating the formation of the ventricular wall and trabecules.

Animals↗
PubMed1980

Postoperative Candida infections of the heart in children: clinicopathologic study of a continuing problem of diagnosis and therapy.

Fungal infections of the heart are infrequent postoperative complications in children, yet, when present are often fatal. Children autopsied at The Johns Hopkins Hospital from 1889 to the present were studied for cardiac fungal infection. Among the 14 children so identified, 8 developed cardiac fungal infection after surgery. All postoperative cardiac infections were caused by Candida species. All were autopsied since 1959. Gastrointestinal surgery was performed in 6 patients and cardiac surgery in 2. Candida infection was not confined to the endocardium; endocarditis developed in 2 patients, pericarditis in 1, and myocarditis in 5. None received cytotoxic agents or corticosteroids. Two patients died from direct cardiac involvement. Other deaths were related to Candida sepsis or bronchopneumonia. A clinical diagnosis of cardiac fungal infection was never made. Prolonged administration of multiple antibiotics, central venous catheterization, prematurity and immune deficiency predisposed to cardiac and systemic candidiasis. Clinical features facilitating early diagnosis are discussed. Removal of central venous catheters infected with Candida did not eliminate the source of continued sepsis, since Candida-laden vegetations related to the catheter adhered to the superior vena cava and endocardial surface. Postoperative cardiac candidiasis is a relatively new and persistent problem of early diagnosis and therapy. The post-surgical pediatric patient has major predisposing factors for cardiac candidiasis, which, if unrecognized, may be a source for continued dissemination or may in itself be the cause of death.

Adolescent↗
PubMed2000

Lack of physiological plasticity in the early chicken embryo exposed to acute hypoxia.

By exposing chicken embryos to hypoxia (10%) acutely (2, 4, and 6 hr) during early development (2, 3, and 4 days) we tested the hypothesis that hypoxia has an impact on embryonic growth and impairs cardiac development at the time cardiac morphogenesis is taking place. After the hypoxic perturbation, the embryos were allowed to develop until day 9, when embryo mass, heart mass, and rate of oxygen consumption were recorded. Four-day-old embryos exposed to 6 hr of hypoxia showed an increased mortality (38.9% versus 18% for controls), indicating the immediate effect of hypoxia on survivability. While only 8% of the controls displayed morphological abnormalities, 3- and 4-day-old embryos exposed for 6 hr showed more frequent developmental abnormalities (25% and 30% respectively). No significant differences in embryo or heart mass were found except in 4-day-old embryos exposed for 2 hr. Mass-specific oxygen consumption was not different between controls and embryos exposed to hypoxia at 2 or 3 days of development, but it was increased in 4-day-old embryos exposed for 4 hr (P < 0.05). These results suggest that an acute hypoxic episode does not have an impact when occurring very early in development (days 2 or 3). However, when the hypoxic episode occurs on day 4, survivability is largely decreased. Considering the lack of permanent effects on the surviving embryos, we suggest that the early embryo resorts to a simple strategy of death or survival, and the individual capacity for survival must be based on interindividual differences rather than the existence of compensatory mechanisms. J. Exp. Zool. 286:450-456, 2000.

Animals↗
PubMed1996

Can cardiac weight predict lung weight in patients with congenital diaphragmatic hernia?

Left ventricular disproportion (decreased left-to-right ventricular internal diameter ratio) has been correlated with fetal or neonatal survival in cases of congenital diaphragmatic hernia (CDH). Because cardiac development is intimately related to lung development in the normally developing fetus, the authors sought to determine whether cardiac weight correlates with lung weight in control and CDH lambs at term. Twenty lambs had CDH created surgically at 80 days' gestation and were sacrificed at term for measurement of lung and heart weight. Nine unoperated lambs served as controls. Analysis of the relationship between heart weight and lung weight was performed for both groups, and regression curves were generated as mean +/- 2 standard deviations (SD) for each group of lambs. All data are expressed in grams. For CDH lambs, the relationship between heart and lung weight is as follows: lung weight = 0.69 x heart weight + 37 g. For control lambs, the equation is: lung weight = -0.004 x heart weight + 135 g. There is no overlap of these regression curves at 2 SD of the mean. The curves differ significantly, and the P value exceeds .05. The results suggest that cardiac weight can be used to predict lung weight in CDH and control lambs at term. The authors speculate that this difference in weight is attributable to underdevelopment of the left ventricle in CDH. Given that left ventricular disproportion has been described as early as the pseudoglandular stage of lung development in human fetuses with CDH, it is hoped that echocardiographic parameters can be used to differentiate the fetuses with adequate lung volume from those whose lung volume is incompatible with extrauterine life. Patients in the latter group may benefit from surgical correction of the diaphragmatic defect in utero.

Analysis of Variance↗
PubMed1998

Ontogeny and regulation of cardiac angiotensin types 1 and 2 receptors during fetal life in sheep.

Previous studies have shown that the expression of cardiac angiotensin II (ANG II) type 1 (AT1) and type 2 (AT2) receptors are developmentally regulated, although factors modulating these receptors have not been well investigated. The present study was designed 1) to characterize the ontogeny of cardiac AT1 and AT2 gene expression during the last third trimester of gestation in fetal sheep and newborn lambs, 2) to determine the influence of ANG II on modulating cardiac AT1 and AT2 gene expression during fetal life, and 3) to investigate the role of AT1 receptor activity on the regulation of AT1 and AT2 mRNA levels during fetal cardiac development. Using sheep AT1 and AT2 cDNA probes, we demonstrated that cardiac AT1 gene expression is relatively unchanged during fetal (90-135 d of gestation, term 145 d) and newborn life. In contrast, cardiac AT2 mRNA expression was high during fetal development and decreased rapidly after birth. Continuous i.v. infusion of ANG II (9.5 nM/h) for 24 h, which raised ANG II levels from 84+/-9 to 210+/-21 pg/mL had no effect on the expression of cardiac AT1 or AT2 mRNA, but increased adrenal and decreased liver AT1 mRNA levels. Administration of the AT1 receptor antagonist losartan (1.2 mg kg(-1) h(-1)) significantly decreased arterial blood pressure in fetuses at 110- and 135-d, but not 95-d gestation. Except for increased AT1 receptor gene expression in the right atrium at 95- and 135-d gestation, and left ventricle at 110-d gestation, cardiac AT1 and AT2 mRNA levels were unaltered by AT1 receptor blockade. In summary, this study demonstrates that cardiac AT2 but not AT1 receptor gene expression is regulated by the transition from fetal to newborn life. Neither ANG II nor blockade of AT1 receptors significantly alter the expression of AT1 or AT2 mRNA in the fetal heart. Endogenous ANG II also appears to significantly contribute to the maintenance of blood pressure homeostasis during the final third of gestation in fetal lambs.

Angiotensin I↗
PubMed2000

Cocaine increases beta-myosin heavy-chain protein expression in cardiac myocytes.

BACKGROUND: As many as 47% of chronic cocaine users develop cardiac ventricular hypertrophy. The presence and degree of cocaine-induced ventricular hypertrophy is not correlated with the use of other substances of abuse such as alcohol or cigarettes. Moreover, this hypertrophy occurs in individuals without sustained increases in arterial blood pressure or heart rate, or increases in the plasma concentration of renin, aldosterone, norepinephrine, or cortisol. Therefore, we investigated whether cocaine, in concentrations commonly found in cocaine users, has any direct effects on the protein content in cardiac ventricular myocytes. We compared the effects of cocaine with norepinephrine, which increases the total protein content, especially beta-myosin heavy-chain contractile protein (beta-MHC), in cardiac ventricular myocytes. METHODS: Experiments were performed on 30-day-old rat ventricular myocytes suspended in culture media and cultured in flasks. In 12 suspension-culture experiments, cocaine or norepinephrine, in doses of 0 (control) or 10(-6) mol/L was added to each culture and the cells were harvested on day 5. In 16 flask-culture experiments, cocaine or norepinephrine was added to each culture on day 7 in doses of 0 (control-vehicle), 10(-7), or 10(-6) mol/L and the cells were harvested on day 10. The total protein content and the myosin protein expression of the myocytes in each culture were determined. Juvenile and adult rat cardiac myosin protein is predominately alpha-myosin heavy-chain protein (alpha-MHC), whereas beta-MHC occurs primarily in fetal rat hearts. RESULTS: In the suspension-culture experiments, cocaine, 10(-6) mol/L, increased the cardiomyocyte total protein concentration by 29% +/- 2% (P <.001) and the beta-MHC expression by 81% +/- 10% (P <.01) in comparison with the control myocytes. Cocaine slightly decreased cardiomyocyte alpha-MHC. Norepinephrine increased the total protein concentration by 21% +/- 3% (P <.001) and the beta-MHC expression by 59% +/- 10% (P <.01), but did not increase alpha-MHC expression. In the flask-culture experiments, cocaine, 10(-6) mol/L, maximally increased the total protein concentration by 28% (P <.001), the protein/cell ratio by 57% +/- 10% (P <.01), and the beta-MHC expression by 85% +/- 8% (P <.01). Cocaine slightly decreased alpha-MHC. Norepinephrine, 10(-6) mol/L, maximally increased the total protein concentration by 35%, the protein/cell ratio by 63% +/- 9% (P <.01), and the expression of beta-MHC by 78% +/- 11% (P <. 01). Norepinephrine did not increase alpha-MHC expression. In 18 separate flask-culture experiments, cocaine, 10(-6) mol/L, was added to the cardiomyocyte cultures after the addition of phentolamine (n = 9), in concentrations of 10(-7) to 10(-5) mol/L, or metoprolol (n = 9), in concentrations of 10(-7) to 10(-5) mol/L. Neither phentolamine nor metoprolol inhibited the cocaine-induced increase in cardiomyocyte total protein content or the expression of beta-MHC. CONCLUSION: Cocaine, similar to norepinephrine, significantly increases the total protein content and the expression of beta-MHC in cardiac ventricular myocytes. In this manner, cocaine may cause cardiac ventricular hypertrophy. This process is not inhibited by alpha- or beta-adrenergic receptor blockade.

Animals↗
PubMed2000

Confocal imaging of early heart development in Xenopus laevis.

Xenopus laevis provides a number of advantages to studies on cardiovascular development. The embryos are fairly large, are easy to obtain, and can develop at ambient temperature in simple buffer solutions. Although classic descriptions of heart development exist, the ability to use whole-mount immunohistochemical methods and confocal microscopy may enhance the ability to understand both normal and experimentally perturbed cardiovascular development. We have started to examine the early stages of cardiac development in Xenopus, seeking to identify antibodies and fixatives that allow easy examination of the developing heart. We have used monoclonal antibodies (mAbs) raised against bovine cardiac troponin T and chicken tropomyosin to visualize cardiac muscle, a goat antibody recognizing bovine type VI collagen to stain the lining of vessels, and the JB3 mAb raised against chicken fibrillin, which allows the visualization of a variety of cardiovascular tissues during early development. Results from embryonic stages 24-46 are presented.

Animals↗
PubMed1997

Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography.

Studies investigating normal and abnormal cardiac development are frequently limited by an inability to assess cardiovascular function within the intact organism. In this work, optical coherence tomography (OCT), a new method of micron-scale, noninvasive imaging based on the measurement of backscattered infrared light, was introduced for the high resolution assessment of structure and function in the developing Xenopus laevis cardiovascular system. Microstructural details, such as ventricular size and wall positions, were delineated with OCT at 16-microm resolution and correlated with histology. Three-dimensional representation of the cardiovascular system also was achieved by repeated cross-sectional imaging at intervals of 25 microm. In addition to structural information, OCT provides high speed in vivo axial ranging and imaging, allowing quantitative dynamic activity, such as ventricular ejection fraction, to be assessed. The sensitivity of OCT for dynamic assessment was demonstrated with an inotropic agent that altered cardiac function and dimensions. Optical coherence tomography is an attractive new technology for assessing cardiovascular development because of its high resolution, its ability to image through nontransparent structures, and its inexpensive portable design. In vivo and in vitro imaging are performed at a resolution approaching that of histopathology without the need for animal killing.

Animals↗
PubMed2004

Wnt11 facilitates embryonic stem cell differentiation to Nkx2.5-positive cardiomyocytes.

Wnt signaling plays a crucial role in the control of morphogenesis in several tissues. Herein, we describe the role of Wnt11 during cardiac differentiation of embryonic stem cells. First, we examined the expression profile of Wnt11 during the course of differentiation in embryoid bodies, and then compared its expression in retinoic acid-treated embryoid bodies with that in untreated. In differentiating embryoid bodies, Wnt11 expression rose along with that of Nkx2.5 expression and continued to increase. When the embryoid bodies were treated with retinoic acid, Wnt11 expression decreased in parallel with the decreased expression of cardiac genes. Further, treatment of embryoid bodies with medium containing Wnt11 increased the expression of cardiac marker genes. Based on these results, we propose that Wnt11 plays an important role for cardiac development by embryoid bodies, and may be a key regulator of cardiac muscle cell proliferation and differentiation during heart development.

Animals↗
PubMed1985

Monoclonal antibodies to desmin: evidence for stage-dependent intermediate filament immunoreactivity during cardiac and skeletal muscle development.

Monoclonal antibodies reactive with desmin (D3 and D76) have been generated and their specificities validated by immunoblots, RIAs, and immunocytochemistry. No cross-reaction with other IFPs has been observed. The McAbs recognized different epitopes but both reside in the amino-terminal rod domain of desmin. Whereas McAb D3 produces a staining pattern characteristic of desmin throughout the development of cardiac and skeletal muscles, McAb D76 was selectively unreactive with certain regions of early (three days in ovo) embryonic cardiac anlage, with cultured cardiac myocytes derived from 7-day-old embryos, and with skeletal myotubes in early stages of myogenesis in vitro. Positive reactivity of D76 was seen at stages of myofibrillogenesis when the sarcomeres assume lateral alignment. Evidence was presented that differential reactivity of D76 did not result from the biosynthesis of a new desmin isoform or the post-translational modification of an existing protein. We suggest that the appearance of D76 immunoreactivity during striated muscle development represents an unmasking of the epitope by some IF-associated protein. Since this transition during skeletal muscle differentiation occurs during lateral alignment of the myofibrils, this antibody may serve as a useful probe for exploring this reorganization of the contractile apparatus during myogenesis and muscle regeneration.

Animals↗
PubMed1992

Electrocardiographic and echocardiographic features of trypanosomiasis in dogs inoculated with North American Trypanosoma cruzi isolates.

Purebred Beagles were inoculated with Trypanosoma cruzi isolates from a North American opossum or armadillo (Tc-W), and dog (Tc-D). Although Tc-D established infection in dogs, the dogs did not develop cardiac abnormalities. Dogs inoculated with Tc-W developed acute myocarditis associated with increases in P-R interval, atrioventricular block, depression of R wave amplitude and shifts in mean electrical axis. Echocardiograms were normal during this stage. Three Tc-W-inoculated dogs died during the acute stage. Following the acute stage, 5 of 8 Tc-W-inoculated dogs entered an indeterminate stage in which ECG changes were minor and echocardiograms were normal. Progression to the chronic stage in 5 of the 8 Tc-W-inoculated dogs was indicated by development of ventricular-based arrhythmias, mainly ventricular premature contractions, between postinoculation days 60 and 170. In some dogs, ventricular premature contractions were multifocal. Electrocardiographic abnormalities progressively degenerated to various forms of ventricular tachycardia. Worsening ECG coincided with loss of left ventricular function as measured by echocardiography. Mean percent ejection fraction and percentage of fractional shortening decreased to 63% and 52% of control values, respectively. The left ventricular free wall (LVFW) thickness decreased and % septal: % LVFW thickening ratio increased, indicating a relative preservation of septal wall motion and LVFW hypokinesis.

Acute Disease↗
PubMed2002

Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis.

Many transcription factors regulate specific temporal-spatial events during cardiac differentiation; however, the mechanisms that regulate such events are largely unknown. Using a modified subtractive hybridization method to identify specific genes that influence early cardiac development, we found that Bop is expressed specifically in cardiac and skeletal muscle precursors before differentiation of these lineages. Bop encodes a protein containing MYND and SET domains, which have been shown to regulate transcription by mediating distinct chromatin modifications. We show that m-Bop is a histone deacetylase-dependent transcriptional repressor. Targeted deletion of Bop in mice disrupted maturation of ventricular cardiomyocytes and interfered with formation of the right ventricle. Normal expression of Hand2, a transcription factor essential for right ventricular development, in cardiomyocyte precursors is dependent upon m-Bop. These results indicate that m-Bop is essential for cardiomyocyte differentiation and cardiac morphogenesis.

Amino Acid Sequence↗