Common signatures for gene expression in postnatal patients with patent arterial ducts and stented arteries

2009 ◽  
Vol 19 (4) ◽  
pp. 352-359 ◽  
Author(s):  
Peter P. Mueller ◽  
Andreas Drynda ◽  
Diane Goltz ◽  
René Hoehn ◽  
Hansjörg Hauser ◽  
...  

AbstractThe detailed molecular processes associated with postnatal remodelling of blood vessels are presently not understood. To characterize the response of the patients undergoing stenting of the patent arterial duct, we harvested samples of vascular tissue during surgical repair. Histological analysis of explanted ducts confirmed the patency of the ducts immediately after birth. As expected, a previously unstented duct that was examined 7 months after birth had become closed and ligamentous. Whole genome expression profiling of these samples showed that a large fraction, over 10%, of the gene sequences examined were expressed differentially between the samples taken from patients with open as opposed to the ligamentous duct. Interestingly, in 2 patients in whom closure was prevented by insertion of stents, one showed an expression profile that was similar to that of the patient initially having an unstented open duct, whereas the other was more closely related to the profile of the patient with a duct that had become ligamentous. Moreover, in 2 specimens obtained from patients with stented pulmonary arteries, a large fraction of the genes that were differentially expressed were identical to the pattern seen in the samples from the patients with open ducts. The gene regulation appeared to be independent of the nature of the respective malformations, and the site of implantation of the stents. These findings suggest that a set of differentially expressed genes are indicative for a transcriptional programme in neonatal remodelling of the arterial duct, which may also take place in patients in whom ductal closure is prevented by stents, or in those with stented pulmonary arteries. The differentially expressed genes included a significant number of extracellular matrix synthetic genes, and could therefore be predictive for vascular remodelling and neointimal formation.

2018 ◽  
Author(s):  
Mirko Pegoraro ◽  
Laura M.M. Flavell ◽  
Pamela Menegazzi ◽  
Perrine Colombi ◽  
Pauline Dao ◽  
...  

AbstractMost animals restrict their activity to a specific part of the day, being diurnal, nocturnal or crepuscular. The genetic basis underlying diurnal preference is largely unknown. Under laboratory conditions, Drosophila melanogaster is crepuscular, showing a bi-modal activity profile. However, a survey of strains derived from wild populations indicated that high variability among individuals exists, with diurnal and nocturnal flies being observed. Using a highly diverse population, we have carried out an artificial selection experiment, selecting flies with extreme diurnal or nocturnal preference. After 10 generations, we obtained highly diurnal and nocturnal strains. We used whole-genome expression analysis to identify differentially expressed genes in diurnal, nocturnal and crepuscular (control) flies. Other than one circadian clock gene (pdp1), most differentially expressed genes were associated with either clock output (pdf, to) or input (Rh3, Rh2, msn). This finding was congruent with behavioural experiments indicating that both light masking and the circadian pacemaker are involved in driving nocturnality. The diurnal and nocturnal selection strains provide us with a unique opportunity to understand the genetic architecture of diurnal preference.


2020 ◽  
Vol 16 (5) ◽  
pp. 635-642 ◽  
Author(s):  
Yuchi Zhang ◽  
Xinyu Wu ◽  
Cong Zhao ◽  
Kai Li ◽  
Yi Zheng ◽  
...  

Background: Molecular characterization of insulin resistance, a growing health issue worldwide, will help to develop novel strategies and accurate biomarkers for disease diagnosis and treatment. Objective: Integrative analysis of gene expression profiling and gene regulatory network was exploited to identify potential biomarkers early in the development of insulin resistance. Methods: RNA was isolated from livers of animals at three weeks of age, and whole-genome expression profiling was performed and analyzed with Agilent mouse 4×44K microarrays. Differentially expressed genes were subsequently validated by qRT-PCR. Functional characterizations of genes and their interactions were performed by Gene Ontology (GO) analysis and gene regulatory network (GRN) analysis. Results: A total of 197 genes were found to be differentially expressed by fold change ≥2 and P < 0.05 in BKS-db +/+ mice relative to sex and age-matched controls. Functional analysis suggested that these differentially expressed genes were enriched in the regulation of phosphorylation and generation of precursor metabolites which are closely associated with insulin resistance. Then a gene regulatory network associated with insulin resistance (IRGRN) was constructed by integration of these differentially expressed genes and known human protein-protein interaction network. The principal component analysis demonstrated that 67 genes in IRGRN could clearly distinguish insulin resistance from the non-disease state. Some of these candidate genes were further experimentally validated by qRT-PCR, highlighting the predictive role as biomarkers in insulin resistance. Conclusions: Our study provides new insight into the pathogenesis and treatment of insulin resistance and also reveals potential novel molecular targets and diagnostic biomarkers for insulin resistance.


2019 ◽  
Author(s):  
Mirko Pegoraro ◽  
Laura M.M. Flavell ◽  
Pamela Menegazzi ◽  
Perrine Colombi ◽  
Pauline Dao ◽  
...  

Abstract Background Most animals restrict their activity to a specific part of the day, being diurnal, nocturnal or crepuscular. The genetic basis underlying diurnal preference is largely unknown. Under laboratory conditions, Drosophila melanogaster is crepuscular, showing a bi-modal activity profile. However, a survey of strains derived from wild populations indicated that high variability among individuals exists, including flies that are nocturnal.Results Using a highly diverse population, we have carried out an artificial selection experiment, selecting flies with extreme diurnal or nocturnal preference. After 10 generations, we obtained highly diurnal and nocturnal strains. We used whole-genome expression analysis to identify differentially expressed genes in diurnal, nocturnal and crepuscular (control) flies. Other than one circadian clock gene ( pdp1 ), most differentially expressed genes were associated with either clock output ( pdf, to ) or input ( Rh3 , Rh2, msn ). This finding was congruent with behavioural experiments indicating that both light masking and the circadian pacemaker are involved in driving nocturnality.Conclusions Our study demonstrates that natural genetic variation in fly wild populations is contributing to substantial variation in diurnal preference. We identified candidate genes associated with diurnality/nocturnality, and the data emerging from our expression analysis and behavioural experiments suggest that both the clock and clock-independent pathways are involved in shaping diurnal preference. The diurnal and nocturnal selection strains provide us with a unique opportunity to understand the genetic architecture of diurnal preference.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yuxi Li ◽  
Peng Wang ◽  
Zhongyu Xie ◽  
Lin Huang ◽  
Rui Yang ◽  
...  

The pathogenesis of dysfunctional immunoregulation of mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) is thought to be a complex process that involves multiple genetic alterations. In this study, MSCs derived from both healthy donors and AS patients were cultured in normal media or media mimicking an inflammatory environment. Whole genome expression profiling analysis of 33,351 genes was performed and differentially expressed genes related to AS were analyzed by GO term analysis and KEGG pathway analysis. Our results showed that in normal media 676 genes were differentially expressed in AS, 354 upregulated and 322 downregulated, while in an inflammatory environment 1767 genes were differentially expressed in AS, 1230 upregulated and 537 downregulated. GO analysis showed that these genes were mainly related to cellular processes, physiological processes, biological regulation, regulation of biological processes, and binding. In addition, by KEGG pathway analysis, 14 key genes from the MAPK signaling and 8 key genes from the TLR signaling pathway were identified as differentially regulated. The results of qRT-PCR verified the expression variation of the 9 genes mentioned above. Our study found that in an inflammatory environment ankylosing spondylitis pathogenesis may be related to activation of the MAPK and TLR signaling pathways.


2021 ◽  
Vol 22 (14) ◽  
pp. 7414
Author(s):  
Dana Dlouha ◽  
Peter Ivak ◽  
Ivan Netuka ◽  
Sarka Benesova ◽  
Zuzana Tucanova ◽  
...  

Studying the long-term impact of continuous-flow left ventricular assist device (CF-LVAD) offers an opportunity for a complex understanding of the pathophysiology of vascular changes in aortic tissue in response to a nonphysiological blood flow pattern. Our study aimed to analyze aortic mRNA/miRNA expression changes in response to long-term LVAD support. Paired aortic samples obtained at the time of LVAD implantation and at the time of heart transplantation were examined for mRNA/miRNA profiling. The number of differentially expressed genes (Pcorr < 0.05) shared between samples before and after LVAD support was 277. The whole miRNome profile revealed 69 differentially expressed miRNAs (Pcorr < 0.05). Gene ontology (GO) analysis identified that LVAD predominantly influenced genes involved in the extracellular matrix and collagen fibril organization. Integrated mRNA/miRNA analysis revealed that potential targets of miRNAs dysregulated in explanted samples are mainly involved in GO biological process terms related to dendritic spine organization, neuron projection organization, and cell junction assembly and organization. We found differentially expressed genes participating in vascular tissue engineering as a consequence of LVAD duration. Changes in aortic miRNA levels demonstrated an effect on molecular processes involved in angiogenesis.


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