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 Doetschman, Jo El J. Schultz

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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 (KATP) 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 (sarcKATP) and mitochondrial (mitoK ATP) KATP 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, sarcKATP and mitoKATP 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 KATP channel activity.

Original languageEnglish (US)
Pages (from-to)124-139
Number of pages16
JournalGrowth Factors
Volume30
Issue number2
DOIs
StatePublished - Apr 2012
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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