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E-GEOD-21096 - Molecular Mechanisms Mediating Preconditioning Following Chronic Ischemia Differ from those in Classical Second Window

Status
Released on 7 April 2010, last updated on 2 May 2014
Organism
Sus scrofa
Samples (20)
Array (1)
Protocols (8)
Description
Ischemic preconditioning represents the most powerful mechanism of cardioprotection. The mechanisms mediating the second window of preconditioning (SWOP) differ from those mediating first window preconditioning. We hypothesized that chronic ischemia induced by repetitive ischemic stimuli would be mediated by yet different molecular mechanisms. Accordingly, conscious, chronically instrumented pigs (n=5/group) were submitted to a protocol of classical SWOP (two 10-min episodes of coronary artery occlusion followed by 24 hr reperfusion) and compared to pigs submitted to repetitive occlusion/reperfusion (RCO) by repeating 6 episodes of SWOP 12 hrs apart, and to a model of repetitive coronary stenosis (RCS), in which 6 episodes of 90 min coronary stenosis were performed 12 hrs apart. Microarray analysis was performed on the three models. There was an 85% homology in gene response between both models of RCO and RCS, whereas SWOP was qualitatively different. Both models of RCO and RCS but not SWOP showed a down-regulation of genes encoding proteins involved in oxidative metabolism, and an up-regulation of genes involved in protein synthesis and unfolded protein response, autophagy, heat shock response, protein secretion, and a strong activation of the NF-κB signaling pathway. Two thirds of the genes regulated in the three models showed a gradual pattern of up- or down-regulation, in which RCO was quantitatively intermediary between RCS and SWOP. Therefore, the regulated genes in response to chronic, repetitive episodes of ischemia differ radically from classical first or second window preconditioning. Four groups of pigs were used for the study, i.e., control (n=5), SWOP (n=5), RCO (n=5), and RCS (n=5). SWOP was induced by two episodes of 10 min coronary artery occlusion (CAO), each followed by 10 min coronary artery reperfusion (CAR). RCO was induced by the same stimulus as SWOP (two cycles of 10 min CAO and 10 min CAR), but repeated six times every 12 hrs. RCS was induced by 90 min low-flow ischemia repeated six times every 12 hrs.
Experiment type
transcription profiling by array 
Contacts
Jiyeon Park <parkji@umdnj.edu>, Athanasios Peppas, Bin Tian, Christophe Depre, Dorothy E Vatner, Lin Yan, Stephen F Vatner
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-21096.idf.txt
Sample and data relationshipE-GEOD-21096.sdrf.txt
Raw data (1)E-GEOD-21096.raw.1.zip
Processed data (1)E-GEOD-21096.processed.1.zip
Array designA-AFFY-75.adf.txt
R ExpressionSetE-GEOD-21096.eSet.r
Links