Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epicardium of the heart originates from a cluster of mesothelial-derived cells that develop beneath the sinus venosus in the embryonic day (E) 9.0-9.5 mouse. The subsequent proepicardium-epicardium transition that forms the epicardial layer of epithelial cells covering the myocardial surface is nearly complete by E10.0-E10.5 and results in a fully covered heart by E11.0. In this study, we show that an established model of congenital heart disease, the retinoid X receptor alpha knockout (RXRalpha-/-) embryo, displays a malformed epicardium. At E10.0-E10.5, the RXRalpha-/- has several large regions of myocardium that remain bare. Furthermore, by E11.5-E12.5, when a complete epithelial layer is formed in the mutant, large regions of the epicardium become distended from the underlying myocardium. Close examination of the E9.5 mutant revealed an elevated apoptosis level within the proepicardial cluster of mesothelial cells. Additionally, among the extracellular matrix proteins analyzed, expression of fibronectin was elevated in the RXRalpha-/- as assessed by immunostaining in paraffin-embedded sections and proepicardial explants. We propose that these events contribute to a developmental delay in the formation of the epicardium, which leads to an abnormal epicardium and ultimately contributes to the cardiac malformations seen in the RXRalpha-/-.
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PMID:Analysis of the proepicardium-epicardium transition during the malformation of the RXRalpha-/- epicardium. 1586 8

Transforming growth factor-beta/bone morphogenetic protein (TGF-beta/BMP) signaling pathway is essential for embryonic and postnatal heart development and remodeling. The intracellular factor Smad4 plays a pivotal role in mediating TGF-beta/BMP signal transduction in the nucleus. To examine the function of Smad4 in embryonic cardiac development during mid-gestation, we specifically deleted the Smad4 gene in embryonic cardiomyocytes using the Cre-LoxP system. Deletion of Smad4 as early as E9.5, led to embryonic lethality between E12.5 and E15.5, and embryos exhibited severe morphological defects in the heart, including a thin compact layer, disorganized trabeculae, and ventricular septum defects (VSD). Smad4 deletion also led to a dramatic decrease in cardiomyocyte proliferation accompanied by downregulation of contractile protein-encoding genes such as alpha-myosin heavy chain, beta-myosin heavy chain, ventricular myosin light chain 2, and alpha-cardiac actin. In addition, deletion of Smad4 resulted in perturbation of TGF-beta/BMP ligand expression and signaling, and defects in expression of several cardiac transcription factor genes such as Nkx2.5, GATA4, and MEF2c. These results provide direct genetic evidences that Smad4 is essential for regulating cardiomyocyte proliferation and differentiation during murine cardiogenesis, and provides new insights into potential causes of congenital heart disease.
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PMID:Essential role of Smad4 in maintaining cardiomyocyte proliferation during murine embryonic heart development. 1786 37

microRNAs (miRNAs) play an important role in regulating normal organ physiology and development. Many miRNAs show spatially and temporally restricted expression patterns during embryogenesis and organogenesis. This study aimed to characterize the miRNA profile of the fetal mouse heart at 4 key time-points [embryonic day (E)12.5, E14.5, E16.5 and E18.5] in its development, by performing a sequencing by oligonucleotide ligation and detection (SOLiD) miRNA screen. The 4 time-points were designated as groups M1 (E18.5), M2 (E16.5), M3 (E14.5) and M4 (E12.5). miRNAs found to have consistent fold-changes of >2.0) between the 4 time-points were selected for further analysis. Ten miRNAs (mmu-miR-23b, mmu-miR-24, mmu-miR-23a, mmu-miR-375, mmu-miR-29a, mmu-miR-93, mmu-miR-21, mmu-miR-25, mmu-let-7b and mmu-miR-27b) that were the most highly expressed in the 4 groups, including the percentage >1% of total read counts, were identified. No miRNA was consistently downregulated or upregulated. There were 16 differentially expressed miRNAs between the later development group (M1+M2) and the early development group (M3+M4), which were validated by quantitative real-time PCR. Several members of the let-7 miRNA cluster (mmu-let-7a/7d/7e/7f) were upregulated in the later development group compared with the early development group. A network analysis of the predicted targets of mmu-let-7a/7d/7e/7f identified 5 target genes (FOXP1, TBX5, HAND1, AKT2 and PPARGC1A), known to be involved in cardiac development. Therefore, this study identified several miRNAs that are abundantly expressed in the developing heart, several of which are differentially expressed in the 4 time-points studied. Findings of this analysis may thus clarify the mechanisms of normal heart development and provide a physiological basis for future studies on congenital heart disease.
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PMID:microRNA expression profiling of the developing mouse heart. 2289 73

Embryonic epicardial cells make an important contribution to cardiac development. However, their proliferation mechanism is still unclear. Epicardial cells from E12.5 fetal hearts were used in our study. Agrin was used to treat these cells. The expression of Aurora B, Ki67 and pH3 was measured by quantitative RT-PCR and immunofluorescence. The proportion of cells in G1/S/G2 phase was determined by flow cytometry. The results showed that agrin significantly increased the expression of ki67, pH3 and Aurora B in epicardial cells. Flow cytometry results showed that agrin significantly increased the proportion of epicardial cells in S phase. However, blocking Yes-associated protein (YAP) significantly downregulated the levels of ki67, pH3 and Aurora B and the proportion of epicardial cells in S phase. Thus, our results suggest that agrin may promote the proliferation of epicardial cells by regulating YAP activity. This may be useful in exploring heart development mechanisms and preventing congenital heart disease.
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PMID:Agrin-YAP promotes the proliferation of epicardial cells. 3313 63