Cardioprotection induced by cardiac-specific overexpression of fibroblast growth factor-2 is mediated by the MAPK cascade

Stacey L. House, Kevin Branch, Gilbert Newman, Thomas Doetschman, Jo El J. Schultz

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Our laboratory showed previously that cardiac-specific overexpression of FGF-2 [FGF-2 transgenic (Tg)] results in increased recovery of contractile function and decreased infarct size after ischemia-reperfusion injury. MAPK signaling is downstream of FGF-2 and has been implicated in other models of cardioprotection. Treatment of FGF-2 Tg and wild-type hearts with U-0126, a MEK-ERK pathway inhibitor, significantly reduced recovery of contractile function after global low-flow ischemia-reperfusion injury in FGF-2 Tg (86 ± 2% vehicle vs. 66 ± 4% U-0126; P < 0.05) but not wild-type (61 ± 7% vehicle vs. 67 ± 7% U-0126) hearts. Similarly, MEK-ERK inhibition significantly increased myocardial infarct size in FGF-2 Tg (12 ± 3% vehicle vs. 31 ± 2% U-0126; P < 0.05) but not wild-type (30 ± 4% vehicle vs. 36 ± 7% U-0126) hearts. In contrast, treatment of FGF-2 Tg and wild-type hearts with SB-203580, a p38 inhibitor, did not abrogate FGF-2-induced cardioprotection from postischemic contractile dysfunction. Instead, inhibition of p38 resulted in decreased infarct size in wild-type hearts (30 ± 4% vehicle vs. 11 ± 2% SB-203580; P < 0.05) but did not alter infarct size in FGF-2 Tg hearts (12 ± 3% vehicle vs. 14 ± 1% SB-203580). Western blot analysis of ERK and p38 activation revealed signaling alterations in FGF-2 Tg and wild-type hearts during early ischemia or reperfusion injury. In addition, MEK-independent ERK inhibition by p38 was observed during early ischemic injury. Together these data suggest that activation of ERK and inhibition of p38 by FGF-2 is cardioprotective during ischemia-reperfusion injury.

Original languageEnglish (US)
Pages (from-to)H2167-H2175
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number5 58-5
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

Keywords

  • Extracellular signal-regulated kinase
  • Ischemia-reperfusion injury
  • Mitogen-activated protein kinase
  • Myocardial infarction
  • Signaling cross talk
  • p38

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Cardioprotection induced by cardiac-specific overexpression of fibroblast growth factor-2 is mediated by the MAPK cascade'. Together they form a unique fingerprint.

  • Cite this