NADPH oxidase-4 (Nox4) is an important reactive oxygen species (ROS) source that is upregulated in the hemodynamically overloaded heart. Our previous studies using global Nox4 knockout (Nox4KO) mice demonstrated a protective role of Nox4 during chronic abdominal aortic banding, involving a paracrine enhancement of myocardial capillary density. However, other authors who studied cardiac-specific Nox4KO mice reported detrimental effects of Nox4 in response to transverse aortic constriction (TAC). It has been speculated that these divergent results are due to cell-specific actions of Nox4 (i.e. cardiomyocyte Nox4 detrimental but endothelial Nox4 beneficial) and/or differences in the model of pressure overload (i.e. abdominal banding versus TAC). This study aimed to: (1) investigate whether the effects of Nox4 on pressure overload-induced cardiac remodeling vary according to the pressure overload model; (2) compare the roles of cardiomyocyte versus endothelial cell Nox4.
Global Nox4KO mice subjected to TAC developed worse cardiac remodeling and contractile dysfunction than wild-type littermates, consistent with our previous results with abdominal aortic banding. Next, we generated inducible cardiomyocyte-specific Nox4 KO mice (Cardio-Nox4KO) and endothelial-specific Nox4 KO mice (Endo-Nox4KO) and studied their responses to pressure overload. Both Cardio-Nox4KO and Endo-Nox4KO developed worse pressure overload-induced cardiac remodeling and dysfunction than wild-type littermates, associated with significant decrease in protein levels of HIF1α and VEGF and impairment of myocardial capillarization.
Cardiomyocyte as well as endothelial cell Nox4 contributes to protection against chronic hemodynamic overload-induced cardiac remodeling, at least in part through common effects on myocardial capillary density.
Pharmacology, Toxicology and Pharmaceutical Science
3
6%
Chemistry
2
4%
Other
5
10%
Unknown
13
27%
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 10 July 2019.
All research outputs
#16,397,602
of 25,988,468 outputs
Outputs from Cardiovascular Research
#3,096
of 4,084 outputs
Outputs of similar age
#192,491
of 339,111 outputs
Outputs of similar age from Cardiovascular Research
#23
of 40 outputs
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