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

Joshua Strom, Qin Chen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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) coronary artery ligation results in myocardial infarction (MI). Young mice surviving MI show minimal signs of heart failure. Mice lacking Nrf2 experience an accelerated progression to heart failure that occurs within 10 days following induction of MI. Nrf2 knockout (Nrf2 KO) mice have a survival rate similar to wild type (WT) mice at 24 h after MI, but a significantly higher mortality rate within 10 days after MI (50% vs 86%). Morphological examination revealed maladaptive remodeling, including cardiac hypertrophy and dilated left ventricle in Nrf2 KO mice, which were absent in WT mice. Measurements of cardiac function revealed increased left ventricular mass and decreases in cardiac output in Nrf2 KO mice. In addition, Nrf2 KO mice show biomarkers of heart failure, such as elevated levels of β-MHC, ANF, and BNP mRNA in the myocardium. These data support that Nrf2 plays an important role in protecting the myocardium from ischemic injury. Lack of Nrf2 leads to rapid development of heart failure.

Original languageEnglish (US)
Pages (from-to)52-58
Number of pages7
JournalToxicology and Applied Pharmacology
Volume327
DOIs
StatePublished - Jul 15 2017

Fingerprint

Heart Failure
Knockout Mice
Myocardial Infarction
Genes
Myocardium
Detoxification
Atrial Natriuretic Factor
Biomarkers
Wounds and Injuries
Cardiomegaly
Transcription Factors
Antioxidants
Cardiac Output
Heart Ventricles
Ligation
Coronary Vessels
Ischemia
Survival Rate
Messenger RNA
Mortality

Keywords

  • Biomarkers
  • Cardiovascular
  • Remodeling
  • Tissue repair
  • Transcription factor

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Loss of Nrf2 promotes rapid progression to heart failure following myocardial infarction. / Strom, Joshua; Chen, Qin.

In: Toxicology and Applied Pharmacology, Vol. 327, 15.07.2017, p. 52-58.

Research output: Contribution to journalArticle

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