Related Experiment Video
Updated: Jul 8, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Involvement of Nox2 NADPH oxidase in adverse cardiac remodeling after myocardial infarction
Yee H Looi1, David J Grieve, Anjana Siva
1Department of Cardiology, King's College London School of Medicine, James Black Centre, 125 Coldharbour Ln, London SE5 9NU, United Kingdom.
Abstract:
Oxidative stress plays an important role in the development of cardiac remodeling after myocardial infarction (MI), but the sources of oxidative stress remain unclear. We investigated the role of Nox2-containing reduced nicotinamide-adenine dinucleotide phosphate oxidase in the development of cardiac remodeling after MI. Adult Nox2(-/-) and matched wild-type (WT) mice were subjected to coronary artery ligation and studied 4 weeks later. Infarct size after MI was similar in Nox2(-/-) and WT mice. Nox2(-/-) mice exhibited significantly less left ventricular (LV) cavity dilatation and dysfunction after MI than WT mice (eg, echocardiographic LV end-diastolic volume: 75.7+/-5.8 versus 112.4+/-12.3 microL; ejection fraction: 41.6+/-3.7 versus 32.9+/-3.2%; both P<0.05). Similarly, in vivo LV systolic and diastolic functions were better preserved in Nox2(-/-) than WT mice (eg, LV dP/dt(max): 7969+/-385 versus 5746+/-234 mm Hg/s; LV end-diastolic pressure: 12.2+/-1.3 versus 18.0+/-1.8 mm Hg; both P<0.05). Nox2(-/-) mice exhibited less cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis; reduced increases in expression of connective tissue growth factor and procollagen 1 mRNA; and smaller increases in myocardial matrix metalloproteinase-2 activity than WT mice. These data suggest that the Nox2-containing reduced nicotinamide-adenine dinucleotide phosphate oxidase contributes significantly to the processes underlying adverse cardiac remodeling and contractile dysfunction post-MI.
Insights
Mice lacking Nox2, an enzyme linked to oxidative stress, showed reduced cardiac remodeling and improved heart function after myocardial infarction (MI). This suggests Nox2 contributes to post-MI heart damage.
Area of Science:
- Cardiovascular Research
- Oxidative Stress Biology
- Molecular Cardiology
Background:
- Oxidative stress is implicated in cardiac remodeling post-myocardial infarction (MI).
- The specific sources of oxidative stress contributing to adverse cardiac remodeling remain largely undefined.
- Nox2-containing NADPH oxidase is a potential key mediator of oxidative stress in the heart.
Purpose of the Study:
- To investigate the role of Nox2-containing NADPH oxidase in cardiac remodeling following MI.
- To determine if inhibiting Nox2 can mitigate adverse cardiac structural and functional changes post-MI.
Main Methods:
- Adult Nox2 knockout (Nox2(-/-)) and wild-type (WT) mice underwent coronary artery ligation to induce MI.
- Cardiac structure and function were assessed 4 weeks post-MI using echocardiography and invasive hemodynamic measurements.
- Histological analyses evaluated infarct size, cardiomyocyte hypertrophy, apoptosis, interstitial fibrosis, and molecular markers of remodeling.
Main Results:
- Infarct size was comparable between Nox2(-/-) and WT mice.
- Nox2(-/-) mice exhibited significantly reduced left ventricular (LV) dilatation and preserved LV systolic and diastolic function compared to WT mice post-MI.
- Nox2 deficiency led to decreased cardiomyocyte hypertrophy, apoptosis, interstitial fibrosis, and reduced expression of fibrotic and matrix metalloproteinase markers.
Conclusions:
- The Nox2-containing NADPH oxidase plays a significant role in adverse cardiac remodeling and contractile dysfunction after myocardial infarction.
- Targeting Nox2 may represent a therapeutic strategy to prevent or treat heart failure post-MI.
Related Concept Videos
01:21Myocarditis I: Introduction
01:28Nitric Oxide Signaling Pathway