Related Experiment Video
Updated: Jul 18, 2026
Use of a Hanging-weight System for Liver Ischemia in Mice
Published on: August 7, 2012
Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice
1Cardiovascular and Pulmonary and Critical Care, Division and the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. syet@rics.bwh.harvard.edu.
Insights
Heme oxygenase-1 (HO-1) overexpression in heart cells protects against heart damage from reduced blood flow and reperfusion. This finding improves recovery of cardiac function, highlighting HO-1
Area of Science:
- Cardiovascular Biology
- Oxidative Stress Research
- Enzyme Function Studies
Background:
- Heme oxygenase (HO)-1 metabolizes heme, producing antioxidant bilirubin and carbon monoxide.
- HO-1 deficiency in mice leads to cardiac oxidative stress and right ventricle infarcts during hypoxia.
- The protective role of HO-1 against cardiac oxidative injury requires further investigation.
Purpose of the Study:
- To determine if cardiac-specific overexpression of heme oxygenase-1 (HO-1) protects the heart from ischemia-reperfusion injury.
- To evaluate the dose-dependent effects of HO-1 on cardiac function recovery after ischemic events.
Main Methods:
- Generation of cardiac-specific transgenic mice with varying levels of HO-1 expression.
- Langendorff preparation to assess isolated heart function recovery post-ischemia.
- In vivo myocardial ischemia-reperfusion experiments to measure infarct size and assess cardiac damage.
Main Results:
- Transgenic mouse hearts demonstrated improved contractile recovery during reperfusion in an HO-1 dose-dependent manner.
- In vivo studies showed significantly reduced infarct size (14.7%) in HO-1 overexpressing mice compared to wild-type (56.5%).
- Hearts with HO-1 overexpression exhibited decreased inflammatory cell infiltration and oxidative damage.
Conclusions:
- Overexpression of HO-1 in cardiomyocytes confers significant protection against ischemia-reperfusion injury.
- HO-1 plays a crucial role in mitigating cardiac damage and improving functional recovery following ischemic events.
- Targeting HO-1 may represent a therapeutic strategy for managing heart conditions involving oxidative stress and ischemia.
Abstract:
Heme oxygenase (HO)-1 degrades the pro-oxidant heme and generates carbon monoxide and antioxidant bilirubin. We have previously shown that in response to hypoxia, HO-1-null mice develop infarcts in the right ventricle of their hearts and that their cardiomyocytes are damaged by oxidative stress. To test whether HO-1 protects against oxidative injury in the heart, we generated cardiac-specific transgenic mice overexpressing different levels of HO-1. By use of a Langendorff preparation, hearts from transgenic mice showed improved recovery of contractile performance during reperfusion after ischemia in an HO-1 dose-dependent manner. In vivo, myocardial ischemia and reperfusion experiments showed that infarct size was only 14.7% of the area at risk in transgenic mice compared with 56.5% in wild-type mice. Hearts from these transgenic animals had reduced inflammatory cell infiltration and oxidative damage. Our data demonstrate that overexpression of HO-1 in the cardiomyocyte protects against ischemia and reperfusion injury, thus improving the recovery of cardiac function.
