Loss of Nrf2 promotes rapid progression to heart failure following myocardial infarction

Nrf2 gene encodes a transcription factor regulating the expression of antioxidant and detoxification genes. We test here whether Nrf2 plays a role for cardiac protection during ischemic injury in an effort to establish Nrf2 as a target for cardiac protection therapies. Cardiac ischemia induced by the left anterior descending (LAD) cor- onary artery ligation results inmyocardial infarction (MI). Young mice survivingMI showminimal signs of heart failure. Mice lacking Nrf2 experience an accelerated progression to heart failure that occurs within 10 days fol- lowing induction of MI. Nrf2 knockout (Nrf2 KO) mice have a survival rate similar to wild type (WT) mice at 24 h afterMI, but a significantly highermortality ratewithin 10 days afterMI (50% vs 86%).Morphological exam- ination revealed maladaptive remodeling, including cardiac hypertrophy and dilated left ventricle in Nrf2 KO mice, which were absent inWT mice. Measurements of cardiac function revealed increased left ventricular mass and decreases in cardiac output inNrf2KOmice. In addition,Nrf2KOmice showbiomarkers ofheart failure, such as elevated levels of β-MHC, ANF, and BNPmRNA in themyocardium. These data support thatNrf2 plays an important role in protecting the myocardiumfromischemic injury. Lack of Nrf2 leads to rapid development of heart failure.