Premium
Ischemia Reperfusion‐Induced microRNAs are Blunted by Ischemic Preconditioning
Author(s) -
Tsutsumi Yasuo M,
Panneerselvam Mathivadhani,
Roth David M,
Patel Hemal H
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1133.3
Subject(s) - microrna , ischemia , reperfusion injury , ischemic preconditioning , microarray , cardioprotection , gene expression , medicine , pharmacology , biology , gene , biochemistry
MicroRNAs (miRNAs) are endogenously expressed, noncoding, small RNA molecules that regulate protein synthesis via degradation of mRNA or inhibition of translation to modulate cellular physiology. Little is known regarding the expression of miRNAs in the heart in response to ischemia/reperfusion (I/R) injury and how this expression is impacted by an ischemic preconditioning (IPC) stimulus. We hypothesized that a distinct expression of miRNA characterizes cardiac injury in response to I/R and IPC is able to normalize this expression towards basal. Methods: miRNA was isolated from hearts of four groups of C57BL/6 mice (n=4 mice/group): control; 30 min ischemia/24 hr reperfusion; 3–5 IPC‐30minischemia/24 hr reperfusion; 3–5 IPC 24 hr reperfusion. The miRNA was hybridized to the NCode miRNA microarray (Invitrogen) and expression analysis performed. miRNA were ranked in order of most highly induced in MI relative to control. Results: Analysis of miRNA expression showed an induction (>50‐fold) of 33 distinct miRNA in hearts exposed to I/R injury relative to control hearts. An IPC stimulus prior to ischemia/reperfusion resulted in a blunted expression (>40%) of 14 of the miRNA induced by I/R alone. IPC prior to I/R resulted in the induction of 14 miRNAs, 50 % of which were not induced in the I/R injury alone group. Conclusion: The results suggest that miRNAs are involved in ischemia/reperfusion injury and IPC limits deleterious miRNA expression. Targeted suppression of miRNAs induced by ischemia/reperfusion injury may represent a novel therapeutic target to mimic IPC.