Fibroblast growth factor-2-induced cardioprotection against myocardial infarction occurs via the interplay between nitric oxide, protein kinase signaling, and ATP-sensitive potassium channels

Janet R. Manning, Gregory Carpenter, Darius R. Porter, Stacey L. House, Daniel A. Pietras, Thomas C Doetschman, Jo El J Schultz

Research output: Contribution to journalArticle

10 Scopus citations


Fibroblast growth factor-2 (FGF2) protects the heart from ischemia-reperfusion (I-R) injury via a vast network of protein kinases. In the heart, downstream effectors of these FGF2-triggered signals have not yet been identified. It is hypothesized that nitric oxide (NO) signaling and ATP-sensitive potassium (K ATP) channel activity are key effectors of protein kinases activated by FGF2-mediated cardioprotection. Hearts with a cardiac-specific overexpression of FGF2 (FGF2 Tg) were subjected to I-R injury in the absence or the presence of selective inhibitors of NO synthase (NOS) isoforms or sarcolemmal (sarcK ATP) and mitochondrial (mitoK ATP) K ATP channels. Multiple NOS isoforms are necessary for FGF2-mediated cardioprotection, and nitrite levels are significantly reduced in FGF2 Tg hearts upon inhibition of protein kinase C or mitogen-activated protein kinases. Likewise, sarcK ATP and mitoK ATP channels are important for cardioprotection elicited by endogenous FGF2. These findings suggest that FGF2-induced cardioprotection occurs via protein kinase-NOS pathways as well as K ATP channel activity.

Original languageEnglish (US)
Pages (from-to)124-139
Number of pages16
JournalGrowth Factors
Issue number2
Publication statusPublished - Apr 2012
Externally publishedYes



  • extracellular signal regulated kinase (ERK)
  • Growth factor
  • ischemia-reperfusion
  • nitric oxide synthase
  • p38
  • PKC
  • transgenic mouse

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

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