Format

Send to

Choose Destination
Toxicol Appl Pharmacol. 2017 Jul 15;327:52-58. doi: 10.1016/j.taap.2017.03.025. Epub 2017 Apr 2.

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

Author information

1
Department of Pharmacology, College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724, United States.
2
Department of Pharmacology, College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724, United States. Electronic address: qchen@email.arizona.edu.

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 10days following induction of MI. Nrf2 knockout (Nrf2 KO) mice have a survival rate similar to wild type (WT) mice at 24h after MI, but a significantly higher mortality rate within 10days 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.

KEYWORDS:

Biomarkers; Cardiovascular; Remodeling; Tissue repair; Transcription factor

PMID:
28373008
DOI:
10.1016/j.taap.2017.03.025
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center