In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.

The free consultation period for this content is over.

It is now only available year-round to ESC Professional Members, Fellows of the ESC, and Young combined Members

NADPH oxidase 4 induces muscle wasting via regulation of NF-E2-related factor 2 in angiotensin ii-infusion mice

Session Poster session 5

Speaker Tomoyasu Kadoguchi

Event : ESC Congress 2017

  • Topic : basic science
  • Sub-topic : Basic Science
  • Session type : Poster Session

Authors : T Kadoguchi (Tokyo,JP), K Shimada (Tokyo,JP), T Shiozawa (Tokyo,JP), S Takahashi (Tokyo,JP), A Hamad (Tokyo,JP), T Aikawa (Tokyo,JP), S Ouchi (Tokyo,JP), K Kitamura (Tokyo,JP), Y Sugita (Tokyo,JP), T Miyazaki (Tokyo,JP), K Akita (Tokyo,JP), K Isoda (Tokyo,JP), H Daida (Tokyo,JP)

Authors:
T. Kadoguchi1 , K. Shimada1 , T. Shiozawa1 , S. Takahashi1 , A. Hamad1 , T. Aikawa1 , S. Ouchi1 , K. Kitamura1 , Y. Sugita1 , T. Miyazaki1 , K. Akita1 , K. Isoda1 , H. Daida1 , 1Juntendo University, Department of Cardiovascular Medicine - Tokyo - Japan ,

Citation:
European Heart Journal ( 2017 ) 38 ( Supplement ), 938

Background: Muscle wasting is involved in chronic heart failure. We have previously revealed that angiotensin II (Ang II), a key mediator of the renin–angiotensin system, directly induced muscle wasting in mice via the activation of NADPH oxidase (Nox), a major source of oxidative stress. In this study, we hypothesized that Nox4 is associated with muscle wasting via regulation of NF-E2-Related Factor 2 (Nrf2) in Ang II-infusion mice.

Methods: Twelve-week old male Nox4 knockout (KO) mice and age-matched male wild-type (WT) mice were used. Either saline (vehicle) or Ang II (1000 ng/kg/min) was infused into WT and Nox4 KO mice via subcutaneously implanted osmotic minipumps for 4 weeks. Experiments were performed in the following 4 groups; WT + vehicle (n=7), Nox4 KO + vehicle (n=8), WT + Ang II (n=7), and Nox4 KO + Ang II (n=8). Skeletal muscles were removed from the lower limbs and used for the analysis of Nox activity, quantitative real-time PCR and western blot.

Results: At baseline, there were no differences in physical characteristics between WT and Nox4 KO mice. However, 4 weeks after Ang II-infusion, WT + Ang II mice showed an increased activation of Nox in the skeletal muscles that was inhibited in Nox4 KO + Ang II mice (p<0.05). Body and lower limb skeletal muscle weight, and myocyte cross-sectional area significantly decreased in WT + Ang II mice compared to WT + vehicle mice (27±1 vs. 31±1 g, 385±3 vs. 438±13 mg, and 1330±30 vs. 2281±150 μm2, respectively; all p values <0.05). These changes were significantly attenuated in Nox4 KO + Ang II mice (30±1 g, 447±9 mg, 2323±22 μm2, respectively; all p values <0.05). Protein expression level of phospho-Akt, a key molecule involved in protein synthesis, decreased in WT + Ang II mice, and muscle RING finger-1 and MAFbx/Atrogin-1, key molecules of protein degradation, significantly increased in WT + Ang II mice compared to WT + vehicle mice. Moreover, gene expression levels of Nrf2 and its regulated genes, and protein expression level of Nrf2 in nuclear fraction significantly decreased in WT + Ang II mice compared to WT + vehicle mice. These parameters were significantly ameliorated in Nox4 KO + Ang II mice (all p values <0.05).

Conclusion: Nox4 induces muscle wasting by Ang II via regulation of Nrf2 pathway, suggesting that the Nox4–Nrf2 axis plays an essential role in the development of muscle wasting.

Get your access to resources

Join now
  • 1ESC Professional Members – access all ESC Congress resources 
  • 2ESC Association Members (Ivory, Silver, Gold) – access your Association’s resources
  • 3Under 40 or in training - with a Combined Membership, access all resources
Join now

Our sponsors

ESC 365 is supported by Bayer, Boehringer Ingelheim and Lilly Alliance, Bristol-Myers Squibb and Pfizer Alliance, Novartis Pharma AG and Vifor Pharma in the form of educational grants. The sponsors were not involved in the development of this platform and had no influence on its content.

logo esc

Our mission: To reduce the burden of cardiovascular disease

Who we are