Endothelial STAT3 plays a critical role in generalized myocardial proinflammatory and proapoptotic signaling

Meijing Wang, Wenjun Zhang, Paul Crisostomo, Troy Markel, Kirstan K. Meldrum, Xin Y. Fu, Daniel R. Meldrum

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Signal transducer and activator of transcription (STAT) 3 is involved in mediating a broad range of biological processes, including cell survival, proliferation, and immune response. Recent evidence has indicated that STAT3 in cardiomyocytes can be activated by ischemic-oxidative stress and exerts cardioprotection in the ischemic heart. There is no information, however, regarding the effect of endothelial cell-derived STAT3 on the myocardial response to ischemia-reperfusion (I/R) injury. We hypothesized that the ablation of the STAT3 gene in endothelial cells would worsen postischemic myocardial function by affecting capillary network integrity, suppressing antiapoptotic signaling. Isolated hearts from wild-type and endothelial cell STAT3 knockout (STAT3KO) mice were subjected to 20 min of global ischemia followed by 60 min of reperfusion. Endothelial cell STAT3 deficiency decreased recovery of myocardial function in response to I/R, which was associated with higher levels of LDH release, decreased activation of myocardial STAT3, and elevated p38 MAPK activation in STAT3 endothelial knockout (KO) hearts. In addition, although no significant apoptosis was observed in wild-type and KO hearts, our results showed more expression of myocardial caspase-8 and more apoptosis in the myocardium around the capillary in STAT3KO mice subjected to I/R. Furthermore, endothelial cell STAT3 ablation resulted in increased myocardial expression of IL-6 and suppressor of cytokine signal 3. This study demonstrates that endothelial cell-derived STAT3 plays an important role in postischemic myocardial function.

Original languageEnglish (US)
Pages (from-to)H2101-H2108
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 1 2007

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Keywords

  • Ischemia-reperfusion
  • Myocardial function
  • Signal transducer and activator of transcription 3

ASJC Scopus subject areas

  • Physiology

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