Cardiac oxidative stress and remodeling following infarction

role of NADPH oxidase

Wenyuan Zhao, Dawn Zhao, Ran Yan, Yao Sun

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Background: There is growing recognition that oxidative stress plays a role in the pathogeneses of myocardial repair/remodeling following myocardial infarction (MI). Nicotinamide adenine denucleotide phosphate (NADPH) oxidase is a major source for cardiac reactive oxygen species production. Herein, we studied the importance of NADPH oxidase in development of cardiac oxidative stress and its induced molecular and cellular changes related to myocardial repair/remodeling. Methods: MI was created by coronary artery ligation in C57/BL (wild type) and NADPH oxidase (gp91phox) knockout mice. Cardiac oxidative stress, inflammatory/fibrogenic responses, apoptosis, and hypertrophy were detected by in situ hybridization, immunohistochemistry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), picrosirius red staining, and image analysis, respectively, at different stages post MI. Results: In wild-type mice with MI, and compared to sham-operated animals, we observed significantly increased gp91phox and 3-nitrotyrosine, a marker of oxidative stress, in the infarcted myocardium; accumulated macrophages and myofibroblasts at the infarct site; abundant apoptotic myocytes primarily at border zones on Day 3; and numerous apoptotic inflammatory/myofibroblasts in the later stages. In addition, we detected significantly increased transforming growth factor β1, tissue inhibitor of metalloprotease 2, and type 1 collagen gene expression; continuously increasing collagen volume in the infarcted myocardium; and hypertrophy in noninfarcted myocardium. Compared to wild-type mice with MI, we did not observe significant difference in infarct size/thickness, cardiac hypertrophy, myocyte apoptosis, inflammatory/fibrogenic responses, as well as cardiac oxidative stress in gp91phox knockout mice. Conclusion: Our findings indicate that during NADPH oxidase deficiency, superoxide production can be compensated by other sources, which leads to cardiac oxidative stress and its related molecular/cellular events in the infarcted heart.

Original languageEnglish (US)
Pages (from-to)156-166
Number of pages11
JournalCardiovascular Pathology
Volume18
Issue number3
DOIs
StatePublished - May 1 2009

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Niacinamide
Adenine
Infarction
Oxidoreductases
Oxidative Stress
Phosphates
Myocardial Infarction
Myocardium
Myofibroblasts
Knockout Mice
Hypertrophy
DNA Nucleotidylexotransferase
Cardiomegaly
Transforming Growth Factors
Metalloproteases
Biotin
Collagen Type I
Cardiac Myocytes
Superoxides
Muscle Cells

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Cardiac oxidative stress and remodeling following infarction : role of NADPH oxidase. / Zhao, Wenyuan; Zhao, Dawn; Yan, Ran; Sun, Yao.

In: Cardiovascular Pathology, Vol. 18, No. 3, 01.05.2009, p. 156-166.

Research output: Contribution to journalArticle

Zhao, Wenyuan ; Zhao, Dawn ; Yan, Ran ; Sun, Yao. / Cardiac oxidative stress and remodeling following infarction : role of NADPH oxidase. In: Cardiovascular Pathology. 2009 ; Vol. 18, No. 3. pp. 156-166.
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