Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.

The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.

N-terminal pro B-type natriuretic peptide (N-BNP) levels in cystic fibrosis patients.

BACKGROUND: The diagnosis of right heart failure and pulmonary hypertension in cystic fibrosis (CF) patients with advanced pulmonary disease is sometimes difficult on clinical grounds alone. B-type natriuretic peptide (BNP) & N-terminal pro-B-type natriuretic peptide (N-BNP) levels were found to be useful in differentiating heart failure from various pulmonary diseases. However, its level was never measured in CF patients. The aim of this study was to measure N-BNP level in CF patients without heart failure. METHODS: The study included 49 patients. Of these, 32 had CF and 17 were control subjects who were matched by age and sex variables to the study group. We looked for a correlation between N-BNP and lung function test, genetic profile, height percentiles, and weight percentiles. N-BNP level was measured using an immunoassay that contains polyclonal antibodies that recognize epitopes located in the N-terminal part of proBNP. RESULTS: N-BNP level among CF patients without heart failure, after age and sex adjustments, was similar to the control group (Median: 47 pg/ml vs. 38 pg/ml, P = 0.248, interquartile range: 33-99 pg/ml vs. 31-76 pg/ml). A correlation between N-BNP level to age was found in both groups (CF: R = -0.398; P = 0.024, CONTROL: R = -0.054; P = 0.024). There was no correlation between N-BNP level to FEV1, O2 saturation and nutritional status. Among CF patients, eight (25%) had a mildly elevated N-BNP level whereas none was found in the control group (P = 0.038). CONCLUSION: We conclude that N-BNP level among CF patients is similar to the normal population and that it has no correlation to lung function impairment. Therefore, measurement of elevated N-BNP level in CF patients might be a predictor to the development of pulmonary hypertension and heart failure.

ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation.

The murine neonatal heart can regenerate after injury through cardiomyocyte (CM) proliferation, although this capacity markedly diminishes after the first week of life. Neuregulin-1 (NRG1) administration has been proposed as a strategy to promote cardiac regeneration. Here, using loss- and gain-of-function genetic tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration. NRG1-induced CM proliferation diminished one week after birth owing to a reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is required for CM proliferation at embryonic/neonatal stages. Induction of a constitutively active ERBB2 (caERBB2) in neonatal, juvenile and adult CMs resulted in cardiomegaly, characterized by extensive CM hypertrophy, dedifferentiation and proliferation, differentially mediated by ERK, AKT and GSK3ß/ß-catenin signalling pathways. Transient induction of caERBB2 following myocardial infarction triggered CM dedifferentiation and proliferation followed by redifferentiation and regeneration. Thus, ERBB2 is both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.

Congenital pulmonary venolobar syndrome: spectrum of helical CT findings with emphasis on computerized reformatting.

The term congenital pulmonary venolobar syndrome refers to a wide spectrum of pulmonary developmental anomalies that may appear singly or in combination. The main components of congenital pulmonary venolobar syndrome are hypogenetic lung (including lobar agenesis, aplasia, or hypoplasia), partial anomalous pulmonary venous return, absence of pulmonary artery, pulmonary sequestration, systemic arterialization of lung, absence of inferior vena cava, and accessory diaphragm. The recent introduction of multisection helical computed tomography (CT), combined with use of advanced postprocessing graphic workstations, allows improved noninvasive delineation of complex congenital anomalies. A single fast (5-15-second) CT scan now enables the radiologist to (a) generate angiogram-like images of the anomalous pulmonary arteries and veins; (b) demonstrate tracheobronchial abnormalities by generating simulated bronchographic or bronchoscopic images; and (c) depict associated parenchymal abnormalities on axial, coronal, or sagittal images, which once represented an important advantage of magnetic resonance imaging over CT. Multisection helical CT is a helpful diagnostic tool in the preoperative evaluation of patients with suspected congenital pulmonary venolobar syndrome.

Left main coronary artery atresia: extremely rare coronary anomaly in an asymptomatic adult and an adolescent soccer player.

Left main coronary artery atresia is a very rare coronary anomaly with only 33 cases reported in the literature, of whom only 1 patient is asymptomatic. Pediatric patients are usually very symptomatic early in life (dyspnea, syncope, failure to thrive, ventricular tachycardia, and sudden death), whereas adult patients begin showing symptoms (angina or sudden death) only at an advanced age. Given the high risk related to the presence of left main coronary artery atresia, and in view of the good results obtained by coronary artery bypass surgery, coronary artery revascularization should always be considered as the possible treatment of choice for establishing adequate myocardial blood flow.

Evaluating the risk of tuberous sclerosis in cases with prenatal diagnosis of cardiac rhabdomyoma.

OBJECTIVE: To evaluate the prenatal parameters that increase the risk of tuberous sclerosis in prenatal management of fetal cardiac tumors suspected as rhabdomyoma. METHODS: The study was a retrospective survey of 18 documented cases in which cardiac rhabdomyoma was suspected during pregnancy. The following parameters were evaluated as possible risk factors associated with tuberous sclerosis: tumor size, isolated or multiple, and family history of tuberous sclerosis. RESULTS: Eighteen documented cases in which cardiac rhabdomyoma was found during pregnancy were evaluated. Of these cases, seven (39%) had proven tuberous sclerosis and 11 were found to be non-associated tuberous sclerosis tumors. When combining the present data with previous series, cases with diagnosis of tuberous sclerosis had equal mean tumor size to those with normal outcome. Family history of tuberous sclerosis in the presence of cardiac rhabdomyoma almost invariably ended with tuberous sclerosis (86%). All other cases with diagnosis of tuberous sclerosis and no family history had all multiple cardiac tumors. CONCLUSION: The present data suggest that 39% of in utero suspected cardiac rhabdomyoma would have tuberous sclerosis. Family history and multifocality remain the strongest predictors of tuberous sclerosis, whereas size of the cardiac tumor can not reliably be used to predict tuberous sclerosis in prenatal counseling.