Ischemic but not pharmacological preconditioning elicits a gene expression profile similar to unprotected myocardium

2004 ◽  
Vol 20 (1) ◽  
pp. 117-130 ◽  
Author(s):  
Rafaela da Silva ◽  
Eliana Lucchinetti ◽  
Thomas Pasch ◽  
Marcus C. Schaub ◽  
Michael Zaugg
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Ischemia Reperfusion ◽  
Expression Patterns ◽  
Principal Component ◽  
Gene Clusters ◽  
Stable Gene ◽  
Transcriptional Responses ◽  
Rat Hearts

Pharmacological (PPC) and ischemic preconditioning (IschPC) provide comparable protection against ischemia in the heart. However, the genomic phenotype may depend on the type of preconditioning. Isolated perfused rat hearts were used to evaluate transcriptional responses to PPC and IschPC in the presence (mediator/effector response) or absence (trigger response) of 40 min of test ischemia using oligonucleotide microarrays. IschPC was induced by 3 cycles of 5 min of ischemia, and PPC by 15 min of 2.1 vol% isoflurane. Unsupervised analysis methods were used to identify gene expression patterns. PPC and IschPC were accompanied by marked alterations in gene expression. PPC and IschPC shared only ∼25% of significantly up- and downregulated genes after triggering. The two types of preconditioning induced a more uniform genomic response after ischemia/reperfusion. Numerous genes separated preconditioned from unprotected ischemic hearts. Three stable gene clusters were identified in the trigger response to preconditioning, while eight stable clusters related to cytoprotection, inflammation, remodeling, and long interspersed nucleotide elements (LINEs) were delineated after prolonged ischemia. A single stable sample cluster emerged from cluster analysis for both IschPC and unprotected myocardium, indicating a close molecular relationship between these two treatments. Principal component analysis revealed differences between PPC vs. IschPC, and trigger vs. mediator/effector responses in transcripts predominantly related to biosynthesis and apoptosis. IschPC and PPC similarly but distinctly reprogram the genetic response to ischemic injury. IschPC elicits a postischemic gene expression profile closer to unprotected myocardium than PPC, which may be therefore more advantageous as therapeutic strategy in cardioprotection.

Gene Expression Profiling of Multiple Patients with Cyclic Thrombocytopenia Reveals Consistent Profile.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 219-219 ◽  
Author(s):  
Ruchira Sood ◽  
Erin Gourley ◽  
Stanley L. Schrier ◽  
Ronald Go ◽  
James L. Zehnder
Keyword(s):  
Gene Expression ◽  
Platelet Count ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Whole Blood ◽  
Gene Clusters ◽  
Underlying Disease ◽  
Multiple Time ◽  
Platelet Counts ◽  
History Of

Abstract Cyclic thrombocytopenia (CTP) is a rare disorder characterized by periodic changes in platelet count. While some previous reports suggest an association with several cytokines, the etiology of this disorder remains poorly characterized. Using DNA microarrays, we examined the gene expression profile in peripheral whole blood at multiple time points encompassing a cycle of platelet counts from two CTP patients. We hypothesized that the variation in gene expression program in whole blood would reflect on the transcriptional changes associated with or perhaps even underlying this disease. Genome-wide cDNA microarray analysis was performed using amplified RNA obtained from 11 and 8 whole blood samples from each patient. The first patient is a 41-year old male with a 2-year history of CTP while the second patient is a 54-year old male with a 3-year history of CTP. The period of both patients’ cycles is roughly 3 weeks. No associated underlying disease has been found in both patients. With a focus on 1500 genes that change 3 fold within each group of samples we observed clusters of gene expression in whole blood that correlate with changing platelet numbers in both patients. Significant variation in expression of a cluster of interferon responsive genes during the platelet count cycle was particularly striking in both samples. Interferon (IFN) therapy is known to suppress platelet counts, and this observation suggests that aberrant IFN levels and signalling could be in part responsible for CTP. At high platelet counts, platelet transcripts were detected in whole blood RNA as inferred by high expression of previously described platelet genes including TBXAS1, TUBB1, OAZ1, SEPT5, several mitochondrial genes, NRGN and F13A1. In addition, gene clusters including known genes as well as previously uncharacterized genes were found to correlate with the peak, increasing or decreasing trends of platelet counts. Briefly, GATA2 and NFE2 expression coincided with the platelet count peak, while Tyk2 and SOCS5 expression was consistent with a rising trend of platelet counts and GATA3 and JAK2 coincided with decreasing trend of platelet counts. These results show gene expression changes associated with CTP in all cell types in whole blood and pave the way for new investigation into regulation of platelet number in a rare and fascinating disease. Gene expression profile of whole blood of two CTP patients with platelet counts ranging from high to low and then increasing again from left to right of each panel Gene expression profile of whole blood of two CTP patients with platelet counts ranging from high to low and then increasing again from left to right of each panel

Gene Expression Profile of Ischemia-reperfusion Injury in Human Lung Transplantatio

CHEST Journal ◽  
2003 ◽  
Vol 124 (4) ◽  
pp. 99S ◽  
Author(s):  
Eric Olson ◽  
Jianping Jin ◽  
William Funkhouser ◽  
Yuechuan Yuan ◽  
Scott Randell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Human Lung ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

Gene-expression signatures as prognostic for relapse in stage I testicular germ cell tumors (TGCT).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 493-493
Author(s):  
Jeremy Howard Lewin ◽  
Philippe L. Bedard ◽  
Robert James Hamilton ◽  
Peter W. M. Chung ◽  
Malcolm J. Moore ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Hierarchical Clustering ◽  
Expression Profile ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Germ Cell Tumors ◽  
Gene Expression Pattern ◽  
Stage I ◽  
Testicular Germ Cell

493 Background: Genomic signatures may compliment pathological features in identifying appropriate patients who may benefit from adjuvant therapy in Stage I (SI) TGCT. This study aimed to identify a gene expression pattern to differentiate between relapsed (R) and non-relapsed (NR) SI TGCT. Methods: Patients with SI non-seminoma (NS) and seminoma (S) were identified from an institutional database from 2000 to 2012. All patients were managed with active surveillance. NR-NS and NR-S patients were defined as having no evidence of relapse after 2 and 3 years of surveillance respectively. Following pathology review, RNA extraction and gene expression analysis was performed on archived paraffin embedded tumor and normal testicular tissue using Illumina Whole Genome DASL Human HT-12 V4 BeadChip. Hierarchical clustering analysis, ANOVA and t-tests were used to evaluate candidate genes and expression patterns that could differentiate NR and R samples. Results: 57 patients (12 R-NS, 15 R-S, 15 NR-NS, 15 NR-S) were identified with median relapse time of 5.6 (2.5-18.1) and 19.3 (4.7-65.3) months in NS and S cohorts respectively. 3 additional normal testis samples were included. Poor prognostic factors were more frequent in R versus NR cases (NS: vascular invasion [5/12 vs 0/15]; S: median size [4cm vs 2.8cm]). Unsupervised hierarchical clustering of 22822 probes randomly separated S from NS, indicating no batch effect. One-way ANOVA revealed 4525 significantly varying probes (p < 0.05) however, no statistically significant gene expression profile differentiated the 4 cohorts. A discriminative gene expression profile between R and NR cases was discovered when combining NS and S samples using 10 (p = 0.03) and 30 (p = 0.03) probe signatures with a 10 fold cross-validation. However, this profile was not observed in the S and NS cohorts individually. Conclusions: A discriminating signature for R and NR was identified for SI testis tumors, but not separately for NS and S. Biological relevance of these signatures is to be determined. Further studies are required to corroborate this profile in NS and S. If validated, these expression patterns could help identify patients beyond standard pathological risk algorithms for optimal management.

Gene expression profile of vascular ischemia-reperfusion injury in rhesus monkeys

Gene ◽  
2016 ◽  
Vol 576 (2) ◽  
pp. 753-762 ◽  
Author(s):  
Ruixi Luo ◽  
Lan Li ◽  
Xiaojiong Du ◽  
Meimei Shi ◽  
Chunguang Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Rhesus Monkeys ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion
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