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

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Abstract

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.

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Acknowledgments

This study was supported by the National Institute of Health (USA) grants HL-56803, HL-69910, and HL-85804 to NM.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut School of Medicine, L-2096, 263, Farmington Avenue, 06032-1110, Farmington, CT, USA

    Mahesh Thirunavukkarasu, Ram Sudheer Adluri, Samson Mathews Samuel, Lijun Zhan & Nilanjana Maulik

  2. Department of Pharmacology, University of Debrecen, Debrecen, Hungary

    Bela Juhasz

  3. Translational Genomics Core, Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, CT, USA

    Anupinder Kaur & Janet Hager

  4. Department of Radiology, Harvard Medical School, Boston, MA, USA

    Gautam Maulik

  5. Department of Surgery, Saint Mary’s Hospital, Waterbury, CT, USA

    Juan A Sanchez

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  1. Mahesh Thirunavukkarasu
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  2. Ram Sudheer Adluri
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  10. Nilanjana Maulik
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Correspondence to Nilanjana Maulik.

Electronic supplementary materials

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Table S1

Top 5 gene networks with high scores (>10) in WTIR versus Nox2−/− IR comparison. (DOC 29 kb)

Table S2

Top 5 gene networks with high scores (>10) in WTIPIR versus Nox2−/− IPIR comparison. (DOC 29 kb)

Table S3

Functional analysis of the differentially expressed genes identified in WTIR versus Nox2−/− IR comparison. (DOC 94 kb)

Table S4

Functional analysis of the differentially expressed genes identified in WTIPIR versus Nox2−/− IPIR comparison. (DOC 115 kb)

Table S5

Pathway analysis of the genes affected in WTIR versus Nox2−/− IR comparison. (DOC 122 kb)

Table S6

Pathway analysis of the genes affected in WTIPIR versus Nox2−/− IPIR comparison. (DOC 126 kb)

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Thirunavukkarasu, M., Adluri, R.S., Juhasz, B. et al. Novel role of NADPH oxidase in ischemic myocardium: a study with Nox2 knockout mice. Funct Integr Genomics 12, 501–514 (2012). https://doi.org/10.1007/s10142-011-0256-x

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