Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital heart disease is the most common type of birth defect with an incidence of 1%. Previously, we described a point mutation in GATA4 that segregated with cardiac defects in a family with autosomal dominant disease. The mutation (G296S) exhibited biochemical deficits and disrupted a novel interaction between Gata4 and Tbx5. To determine if Gata4 and Tbx5 genetically interact in vivo, we generated mice heterozygous for both alleles. We found that nearly 100% of mice heterozygous for Gata4 and Tbx5 were embryonic or neonatal lethal and had complete atrioventricular (AV) septal defects with a single AV valve and myocardial thinning. Consistent with this phenotype, Gata4 and Tbx5 are co-expressed in the developing endocardial cushions and myocardium. In mutant embryos, cardiomyocyte proliferation deficits were identified compatible with the myocardial hypoplasia. Similar to Gata4, Gata6 and Tbx5 are co-expressed in the embryonic heart, and the transcription factors synergistically activate the atrial natiuretic factor promoter. We demonstrate a genetic interaction between Gata6 and Tbx5 with an incompletely penetrant phenotype of neonatal lethality and thin myocardium. Gene expression analyses were performed on both sets of compound heterozygotes and demonstrated downregulation of alpha-myosin heavy chain only in Gata4/Tbx5 heterozygotes. These findings highlight the unique genetic interactions of Gata4 and Gata6 with Tbx5 for normal cardiac morphogenesis in vivo.
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PMID:Interaction of Gata4 and Gata6 with Tbx5 is critical for normal cardiac development. 1908 12

Congenital heart disease is the leading cause of infant death in the United States with over 36,000 newborns affected each year. Despite this growing problem there are few mechanical circulatory support devices designed specifically for pediatric and neonate patients. Previous research has been done investigating pediatric ventricular assist devices (PVADs) assuming blood to be a Newtonian fluid in computational fluid dynamics (CFD) simulations, ignoring its viscoelastic and shear-thinning properties. In contrast to adult VADs, PVADs may be more susceptible to hemolysis and thrombosis due to altered flow into the aorta, and therefore, a more accurate blood model should be used. A CFD solver that incorporates a modified Oldroyd-B model designed specifically for pediatric blood is used to investigate important hemodynamic parameters in a pediatric aortic model under pulsatile flow conditions. These results are compared to Newtonian blood simulations at three physiological pediatric hematocrits. Minor differences are seen in both velocity and wall shear stress (WSS) during early stages of the cardiac cycle between the Newtonian and viscoelastic models. During diastole, significant differences are seen in the velocities in the descending aorta (up to 12%) and in the aortic branches (up to 30%) between the two models. Additionally, peak WSS differences are seen between the models throughout the cardiac cycle. At the onset of diastole, peak WSS differences of 43% are seen between the Newtonian and viscoelastic model and between the 20 and 60% hematocrit viscoelastic models at peak systole of 41%.
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PMID:Hemodynamics in a Pediatric Ascending Aorta Using a Viscoelastic Pediatric Blood Model. 2615 60