Project description:Coarctation of the aorta (CoA) is a relatively common congenital heart defect that affects males more often than females. The underlying causes are not known, but a combination of genetic factors and abnormalities linked to embryonic development is suspected. There are only a few studies of the underlying molecular mechanisms in CoA. The aim of the current study was to expand our understanding of the pathogenesis of CoA by characterizing the transcriptome of the coarctation area.
Project description:"Background: The ascomycete Fusarium fujikuroi causes “bakanae” disease of rice due to its ability to produce gibberellins (GA), but is also known for producing a broad spectrum of other secondary metabolites, (SM) such as pigments and harmful mycotoxins. Biosynthesis of multiple SM is regulated by nitrogen availability. The global GATA transcription factors (TF) AreA and AreB were shown to play key roles in this nitrogen-dependent regulation. Recently, we have shown that AreA activates the transcription of AREB, but not vice versa. Both regulators interact in the nucleus, indicating a complex regulatory interplay between both regulators. Results: We performed transcriptome and proteome analyses of the wild type and ΔAREA and ΔAREB mutants under nitrogen limiting and sufficient conditions. Microarray analysis revealed that each transcription factor regulates a total set of about 4,200 genes under nitrogen limiting conditions. Gene enrichment analysis revealed that significantly up- and down-regulated genes belong to functional classes of primary/secondary metabolism, transporters, cell defense/virulence and transcription. Under nitrogen excess, AreA is not active as a transcriptional regulator, while AreB affects expression of about 4,400 genes. Both transcription factors regulate a common set of about 2,100 genes, often coordinately either as positive or as negative regulators. Our proteomics analysis identified 446 AreA-regulated and 386 AreB-regulated proteins under nitrogen limitation and 138 AreA-regulated and 447 AreB-regulated proteins under nitrogen sufficiency, respectively. Comparison of the proteome and transcriptome data indicates that both GATA-factors not only regulate expression of target genes but also affect protein abundance by post-transcriptional regulations, for example on enzymes involved in glutamate cycling, as well as histone acetylation at some of the target SM gene clusters. Conclusion: This study provides novel insights into the AreA- and AreB-mediated regulation network on a cellular scale. Microarray analysis clearly demonstrated that both GATA-factors are major regulators of alternate nitrogen assimilatory pathways and secondary metabolism. Moreover, proteome analysis of the AREA and AREB deletion mutants showed that both TF are global players interconnecting carbon and nitrogen regulation. They mainly act as mutualistic, but also antagonistic regulators and operate by transcriptional and post-transcriptional regulations and epigenetic modifications." (Abstract taken from manuscript)
Project description:Purpose: The aim of this study is to have a fullscape of molecular pathology of Stanford type A aortic dissection Methods: All TAAD patients under consideration underwent an ascending aortic replacement surgery during a cardiopulmonary bypass. The normal ascending aortic tissue samples were obtained from patients undergoing coronary artery bypass grafting surgery (CABG) without any aortic diseases. We selected 20 samples (10 TAAD and 10 normal) for the whole transcriptome sequencing. Total RNA was extracted from each sample using TRIzol Reagent (ThermoFisher) and was stored in 1 mL of 75% ethanol at -80 ℃ until further usage. Conclusions: We identified exaggerated autophagy as a molecular biomarker for aortic dissection. We also predicted 10 hub genes and an HIF1A-ATG3 axis which could provide new insights in understanding aortic dissection.
Project description:The objective of the current investigation was to use microarray techniques to quantify differentially expressed genes (DEGs) in the upstream aorta subjected to high arterial BP after surgical induction of CoA, and restoration of normal arterial BP after its correction. DEGs may offer additional insight into potential mechanisms of persistent CV morbidity despite successful surgical repair. Male New Zealand white rabbits ~10 weeks old and weighing ~1.0 kg randomly underwent proximal dAo CoA. A 20 mmHg BP gradient was imposed using silk (permanent) or Vicryl (degradable) suture to mimic untreated CoA and surgically corrected CoA, respectively. Rabbits develop a pronounced stenosis and accompanying elevated BP as a stimulus for arterial remodeling within one week. Degradation of Vicryl suture in the corrected group restores aortic diameter close to normal, but with modest residual narrowing. Non-experimental rabbits were designated as a control group. This results in a statistically significant increase in mean, systolic and pulse BP proximal to the coarctation for CoA as compared to both control and corrected rabbits. A ~4 mm circumferential region from the proximal aorta between the coarctation site and left subclavian artery was excised at harvest (32 weeks of age) and frozen. Frozen samples (n=4/group) were shipped overnight to Arraystar, Inc (Rockville, MD) for microarray analysis.
Project description:The aim of the present study was to gain insights on the pathological process of Calcific Aortic Valve Disease in CHIP carriers. To uncover molecular pathways that could link CHIP to CAVD, we exanimated the aortic valve transcriptome from CHIP, non-CHIP patients, or non-calcific controls with RNAseq.
Project description:Exaggerated autophagy as molecular characterization of Stanford type A aortic dissection: A transcriptome analysis of human ascending aortic tissues