Cardioprotection by ischemic postconditioning is lost in aged and STAT3-deficient mice.

Abstract:

:The cardioprotection by ischemic preconditioning is lost in aged wild-type and in STAT3 (signal transducer and activator of transcription 3)-deficient mice. The aim of the present study was to analyze whether or not ischemic postconditioning (iPoco) was effective in aged mice hearts and whether iPoco was dependent on STAT3. Young (3 months) and aged (>13 months) C57Bl6/J mice underwent 30 minutes of ischemia and 2 hours of reperfusion without or with iPoco (3 cycles of 10 seconds of ischemia/10 seconds of reperfusion [3x10] or 5 cycles of 5 seconds of ischemia/5 seconds of reperfusion [5x5] at the beginning of reperfusion). In young mice, both iPoco3x10 and iPoco5x5 reduced infarct size (IS), whereas in aged mice, only iPoco5x5 was effective in reducing IS. In young mice, iPoco3x10 increased the phosphorylated over total STAT3 (phosphorylated STAT3/STAT3) ratio at 10 minutes of reperfusion in the postconditioned anterior wall compared with the control posterior wall. In aged mice hearts, total STAT3 and phosphorylated STAT3/STAT3 in the anterior wall at reperfusion were reduced compared with young mice hearts. In young mice hearts subjected to iPoco3x10 but pretreated with the JAK-2 inhibitor AG-490, phosphorylated STAT3/STAT3 was reduced in the anterior wall compared with untreated young mice hearts, and IS reduction by iPoco3x10 was abolished. Furthermore, in young mice with a cardiomyocyte-restricted deletion of STAT3, iPoco3x10 failed to reduce IS, whereas iPoco5x5 reduced IS. Thus, cardioprotection by iPoco is dependent on the postconditioning protocol in aged and STAT3-deficient hearts. The reduced levels of STAT3 with increasing age may contribute to the age-related loss of iPoco.

journal_name

Circ Res

journal_title

Circulation research

authors

Boengler K,Buechert A,Heinen Y,Roeskes C,Hilfiker-Kleiner D,Heusch G,Schulz R

doi

10.1161/CIRCRESAHA.107.164699

subject

Has Abstract

pub_date

2008-01-04 00:00:00

pages

131-5

issue

1

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.107.164699

journal_volume

102

pub_type

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