Novel role of NADPH oxidase in ischemic myocardium: a study with Nox2 knockout mice

Funct Integr Genomics. 2012 Aug;12(3):501-14. doi: 10.1007/s10142-011-0256-x. Epub 2011 Oct 29.


Several potential sources of reactive oxygen species (ROS) in cells exist. One source is NADPH oxidase, which is especially important for superoxide radical production. Nox2 is a primary regulatory subunit of NADPH oxidase. In the present study, we examined the role of ROS and NADPH oxidase in ischemic preconditioning (IP)-mediated cardioprotection by using Nox2(-/-) mice. Both wild-type (WT) and Nox2(-/-) mice were subjected to either 30 min of ischemia followed by 2 h of reperfusion (IR) or IP prior to 30 min ischemia and 2 h of reperfusion. Reduction in left ventricular developed pressure (60.1 versus 63 mmHg), dp/dt (max) (893 versus 1,027 mmHg/s), and aortic flow (0.9 versus 1.8 ml/min) was observed in Nox2(-/-)IPIR compared to WTIPIR along with increased infarct size (33% versus 22%) and apoptosis after 120 min of reperfusion. Differentially regulated genes were demonstrated by comparing gene expression in WTIPIR versus Nox2(-/-) IPIR hearts. Selected differentially regulated genes such as β-catenin, SRPK3, ERDR1, ACIN1, Syntaxin-8, and STC1 were validated by real-time PCR. Taken together, this is the first report identifying important, differentially expressed genes during ischemic preconditioning in Nox2(-/-) mice by using microarray analysis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Arterial Pressure
  • Gene Expression Profiling
  • Gene Expression Regulation
  • In Vitro Techniques
  • Ischemic Preconditioning, Myocardial / methods*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Myocardial Ischemia / enzymology*
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / pathology
  • Myocardial Reperfusion / methods
  • Myocytes, Cardiac / pathology
  • NADPH Oxidase 2
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism*
  • Reactive Oxygen Species / metabolism
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Tissue Array Analysis
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • CTNNB1 protein, mouse
  • Membrane Glycoproteins
  • Reactive Oxygen Species
  • beta Catenin
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases