The transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2) controls a network of cytoprotective genes. Neither how Nrf2 is activated in the heart under hemodynamic overload nor its role and mechanism of action are known. This study aimed to investigate the activation and role of Nrf2 during chronic cardiac pressure overload. We first compared the responses of Nrf2(-/-) mice and wild-type littermates to chronic pressure overload. Hearts of Nrf2(-/-) mice showed impaired antioxidant gene expression, increased hypertrophy, and worse function compared with those of wild-type littermates after overload. Hearts of Nrf2(-/-) mice had increased mitochondrial DNA damage, a caspase 8/BH3-interacting domain death agonist-related cleavage of mitochondrial apoptosis-inducing factor, nuclear DNA damage, and cell death. Nrf2 activation was under the control of the endogenous reactive oxygen species-generating enzyme nicotinamide adenine dinucleotide phosphate oxidase-4, both in vivo and in vitro. In mice with cardiac-specific overexpression of nicotinamide adenine dinucleotide phosphate oxidase-4, Nrf2 deletion significantly attenuated their protective phenotype during chronic pressure overload. This study identifies nicotinamide adenine dinucleotide phosphate oxidase-4-dependent upregulation of Nrf2 as an important endogenous protective pathway that limits mitochondrial damage and apoptosis-inducing factor-related cell death in the heart under hemodynamic overload.
Pharmacology, Toxicology and Pharmaceutical Science
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3%
Immunology and Microbiology
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3%
Other
1
3%
Unknown
11
31%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 December 2014.
All research outputs
#16,720,137
of 25,371,288 outputs
Outputs from Hypertension
#5,282
of 7,138 outputs
Outputs of similar age
#210,111
of 359,692 outputs
Outputs of similar age from Hypertension
#48
of 86 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,138 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
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We're also able to compare this research output to 86 others from the same source and published within six weeks on either side of this one. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
