Heart, Lung and Circulation
Original Article| Volume 14, ISSUE 1, P36-43, March 2005

Ischemic Preconditioning at a Distance: Altered Gene Expression in Mouse Heart and Other Organs Following Brief Occlusion of the Mesenteric Artery

      Remote ischemic preconditionining (IPC) has been defined as a brief episode of ischemia/reperfusion in an organ that protects another remote organ from the damage induced by subsequent and prolonged ischemia. As yet, no study has been conducted with the purpose of elucidating a precise association between remote IPC and patterns of gene-transcription in cardiac tissue. In this study, using a cDNA microarray, we analyzed the gene expression profile in murine heart at 24 h after brief cycles of occlusion of the superior mesenteric artery. The profile revealed that IPC induces significant levels of expression of many genes known to be associated with the stress response, redox regulation, growth and metabolism, DNA repair and other functions. The result of cDNA microarray profile from heart was also compared with those from other organs (lung, kidney and intestine). The genes identified in the expression profile may be associated with remote IPC induced late phase organ protection.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Heart, Lung and Circulation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Murry C.E.
        • Jennings R.B.
        • Reimer K.A.
        Preconditioning with ischemia: a delay of lethal injury in ischemic myocardium.
        Circulation. 1986; 74: 1124-1136
        • Pell T.J.
        • Baxter G.F.
        • Yellon D.M.
        • Drew G.M.
        Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels.
        Am J Physiol. 1998; 275: H1542-H1547
        • Ates E.
        • et al.
        Renal protection by brief liver ischemia in rats.
        Transplantation. 2002; 74: 1247-1251
        • Rizvi A.
        • et al.
        Increased protein synthesis is necessary for the development of late preconditioning against myocardial stunning.
        Am J Physiol. 1999; 277: H874-H884
        • Bolli R.
        The late phase of preconditioning.
        Circ Res. 2000; 87: 972-983
        • Baxter G.F.
        • Goma F.M.
        • Yellon D.M.
        Characterisation of the infarct-limiting effect of delayed preconditioning: timecourse and dose-dependency studies in rabbit myocardium.
        Basic Res Cardiol. 1997; 92: 159-167
        • Gray M.O.
        • Karliner J.S.
        • Mochly-Rosen D.
        A selective epsilon-protein kinase C antagonist inhibits protection of cardiac myocytes from hypoxia-induced cell death.
        J Biol Chem. 1997; 272: 30945-30951
        • Park K.M.
        • Chen A.
        • Bonventre J.V.
        Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment.
        J Biol Chem. 2001; 276: 11870-11876
        • Latchman D.S.
        Heat shock proteins and cardiac protection.
        Cardiovasc Res. 2001; 51: 637-646
        • Wang Y.
        • et al.
        Ischemic preconditioning upregulates inducible nitric oxide synthase in cardiac myocyte.
        J Mol Cell Cardiol. 2002; 34: 5-15
        • McLaughlin B.
        • et al.
        Caspase 3 activation is essential for neuroprotection in preconditioning.
        Proc Natl Acad Sci. 2003; 100: 715-720
        • Lalu M.M.
        • et al.
        Preconditioning decreases ischemia/reperfusion-induced release and activation of matrix metalloproteinase-2.
        Biochem Biophys Res Commun. 2002; 296: 937-941
        • Bernaudin M.
        • Tang Y.
        • Reilly M.
        • Petit E.
        • Sharp F.R.
        Brain genomic response following hypoxia and re-oxygenation in the neonatal rat. Identification of genes that might contribute to hypoxia-induced ischemic tolerance.
        J Biol Chem. 2002; 277: 39728-39738
        • Onody A.
        • et al.
        Effect of classic preconditioning on the gene expression pattern of rat hearts: a DNA microarray study.
        FEBS Lett. 2003; 536: 35-40
        • Przyklenk K.
        • Darling C.E.
        • Dickson E.W.
        • et al.
        Cardioprotection ‘Outside the Box’: the evolving paradigm of remote preconditioning.
        Basic Res Cardiol. 2003; 98: 149-157
        • Yamashita N.
        • Hoshida S.
        • Taniguchi N.
        • et al.
        A “Second window of protection” occurs 24 h after ischemic preconditioning in the rat heart.
        J Mol Cell Cardiol. 1998; 30: 1181-1189
        • Sandhu R.
        • Diaz R.J.
        • Mao G.D.
        • Wilson G.J.
        Ischemic preconditioning: differences in protection and susceptibility to blockade with single-cycle versus multicycle transient ischemia.
        Circulation. 1997; 96: 984-995
        • Patel H.H.
        • Moore J.
        • Hsu K.A.
        • Gross G.J.
        Cardioprotection at a distance: mesenteric artery occlusion protects the myocardium via an opioid sensitive mechanism.
        J Mol Cell Cardiol. 2002; 34: 1317-1323
        • Chomczynski P.
        • Sacchi N.
        Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction.
        Anal Biochem. 1987; 162: 156-159
        • Eisen M.B.
        • Spellman P.T.
        • Brown P.O.
        • Botstein D.
        Cluster analysis and display of genome-wide expression patterns.
        Proc Natl Acad Sci. 1998; 95: 14863-14868
        • Eisen M.B.
        • Brown P.O.
        DNA arrays for analysis of gene expression.
        Methods Enzymol. 1999; 303: 179-205
        • Lu R.
        • Li Y.J.
        • Deng H.W.
        Evidence for calcitonin gene-related peptide-mediated ischemic preconditioning in the rat heart.
        Regul Pept. 1999; 82: 53-57
        • Prado M.A.
        • Evans-Bain B.
        • Dickerson I.M.
        Receptor component protein (RCP): a member of a multi-protein complex required for G-protein-coupled signal transduction.
        Biochem Soc Trans. 2002; 30: 460-464
        • Prohaska J.R.
        • Oh S.H.
        • Hoekstra W.G.
        • Ganther H.E.
        Glutathione peroxidase: inhibition by cyanide and release of selenium.
        Biochem Biophys Res Commun. 1977; 74: 64-71
        • Ketterer B.
        Protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis.
        Mutat Res. 1988; 202: 343-361
        • Cho S.G.
        • Lee Y.H.
        • Park H.S.
        • et al.
        Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1.
        J Biol Chem. 2001; 276: 12749-12755
        • Iwata F.
        • Joh T.
        • Ueda F.
        • Yokoyama Y.
        • Itoh M.
        Role of gap junctions in inhibiting ischemia-reperfusion injury of rat gastric mucosa.
        Am J Physiol. 1998; 275: G883-G888
        • Simon M.
        • et al.
        Expression of bone morphogenetic protein-7 mRNA in normal and ischemic adult rat kidney.
        Am J Physiol. 1999; 276: F382-F389
        • Helm G.A.
        • Alden T.D.
        • Sheehan J.P.
        • Kallmes D.
        Bone morphogenetic proteins and bone morphogenetic protein gene therapy in neurological surgery.
        Neurosurgery. 2000; 46: 1213-1222
        • Liu Y.
        • et al.
        The effect of bone morphogenetic protein-7 (BMP-7) on functional recovery, local cerebral glucose utilization and blood flow after transient focal cerebral ischemia in rats.
        Brain Res. 2001; 905: 81-90
        • Truettner J.
        • et al.
        Effect of ischemic preconditioning on the expression of putative neuroprotective genes in the rat brain.
        Mol Brain Res. 2002; 103: 106-115
        • Onody A.
        • et al.
        Effect of classic preconditioning on the gene expression pattern of rat hearts: a DNA microarray study.
        FEBS Lett. 2003; 536: 35-40
        • Simkhovich B.
        • et al.
        Gene expression profiling—a new approach in the study of myocardial ischemia.
        Cardiovasc Pathol. 2003; 12: 180-185
        • Tran H.
        • et al.
        DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein.
        Science. 2002; 296: 530-534
        • Kops G.J.
        • et al.
        Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress.
        Nature. 2002; 419: 316-321
        • Medema R.H.
        • Kops G.J.
        • Bos J.L.
        • Burgering B.M.
        AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.
        Nature. 2000; 404: 782-787