title: The remote ischemic preconditioning stimulus modifies gene expression in mouse myocardium.
abstract: BACKGROUND
  We have recently demonstrated that remote ischemic preconditioning reduces ischemia-reperfusion injury in animal models. The mechanisms by which the remote ischemic preconditioning stimulus exerts its effect remain to be fully defined, and its effect on myocardial gene expression is unknown. We tested the hypothesis that remote ischemic preconditioning modifies myocardial gene expression immediately after the remote ischemic preconditioning stimulus (early phase) and 24 hours later (late phase).
  
  
  METHODS
  Twenty male (C57BL/6) 10- to 12-week-old mice were randomized into 4 groups: group 1 (control, early phase; n = 5), group 2 (remote ischemic preconditioning, early phase; n = 5), group 3 (control, late phase; n = 5), and group 4 (remote ischemic preconditioning, late phase; n = 5). Groups 2 and 4 underwent remote ischemic preconditioning induced by 6 cycles of 4 minutes of occlusion and 4 minutes of reperfusion of the femoral artery. Groups 1 and 2 were killed 15 minutes after completion of sham procedure or remote ischemic preconditioning, and the hearts were removed and frozen in liquid nitrogen. Groups 3 and 4 were killed 24 hours after remote ischemic preconditioning, and the hearts were harvested in the same fashion. Gene expression was assessed by using the Affymetrix MG-430A chip (Affymetrix, Santa Clara, Calif).
  
  
  RESULTS
  Data filtering (P < .05, analysis of variance) and hierarchic 2-way clustering identified significant differences in gene expression among the 4 groups. Genes involved in protection against oxidative stress (eg, Hadhsc, Prdx4, and Fabp4) and cytoprotection (Hsp73) were upregulated, whereas many proinflammatory genes (eg, Egr-1 and Dusp 1 and 6) were suppressed.
  
  
  CONCLUSIONS
  A simple remote ischemic preconditioning stimulus modifies myocardial gene expression by upregulating cardioprotective genes and suppressing genes potentially involved in the pathogenesis of ischemia-reperfusion injury.
authors.affiliation: Division of Cardiovascular Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Igor E
authors.initials: IE
authors.lastname: Konstantinov
authors.forename: Sara
authors.initials: S
authors.lastname: Arab
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: John G
authors.initials: JG
authors.lastname: Coles
authors.forename: Cathy
authors.initials: C
authors.lastname: Boscarino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mori
authors.forename: Eva
authors.initials: E
authors.lastname: Cukerman
authors.forename: Fayez
authors.initials: F
authors.lastname: Dawood
authors.forename: Michael M H
authors.initials: MM
authors.lastname: Cheung
authors.forename: Mikiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Peter P
authors.initials: PP
authors.lastname: Liu
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Redington
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium